-----BEGIN PRIVACY-ENHANCED MESSAGE-----
Proc-Type: 2001,MIC-CLEAR
Originator-Name: webmaster@www.sec.gov
Originator-Key-Asymmetric:
 MFgwCgYEVQgBAQICAf8DSgAwRwJAW2sNKK9AVtBzYZmr6aGjlWyK3XmZv3dTINen
 TWSM7vrzLADbmYQaionwg5sDW3P6oaM5D3tdezXMm7z1T+B+twIDAQAB
MIC-Info: RSA-MD5,RSA,
 E/oIf/WmLlTDJ8xikewIlhGhpMd3S9T2cRRmvRYSm3KLnyGKcCpiGhEdFN2dUzYx
 YHI1PEKgD5Rd2WemtqbOPA==

<SEC-DOCUMENT>0000874015-05-000021.txt : 20050706
<SEC-HEADER>0000874015-05-000021.hdr.sgml : 20050706
<ACCEPTANCE-DATETIME>20050706175520
ACCESSION NUMBER:		0000874015-05-000021
CONFORMED SUBMISSION TYPE:	4
PUBLIC DOCUMENT COUNT:		2
CONFORMED PERIOD OF REPORT:	20050701
FILED AS OF DATE:		20050706
DATE AS OF CHANGE:		20050706

ISSUER:		

	COMPANY DATA:	
		COMPANY CONFORMED NAME:			ISIS PHARMACEUTICALS INC
		CENTRAL INDEX KEY:			0000874015
		STANDARD INDUSTRIAL CLASSIFICATION:	PHARMACEUTICAL PREPARATIONS [2834]
		IRS NUMBER:				330336973
		STATE OF INCORPORATION:			DE
		FISCAL YEAR END:			1231

	BUSINESS ADDRESS:	
		STREET 1:		1896 RUTHERFORD ROAD
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92008
		BUSINESS PHONE:		7609319200

	MAIL ADDRESS:	
		STREET 1:		1896 RUTHERFORD ROAD
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92008

REPORTING-OWNER:	

	OWNER DATA:	
		COMPANY CONFORMED NAME:			MUTO FREDERICK T
		CENTRAL INDEX KEY:			0001181560
		STATE OF INCORPORATION:			DE
		FISCAL YEAR END:			1231

	FILING VALUES:
		FORM TYPE:		4
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	000-19125
		FILM NUMBER:		05941826

	BUSINESS ADDRESS:	
		STREET 1:		2292 FARADAY AVENUE
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92008
		BUSINESS PHONE:		760-931-9200

	MAIL ADDRESS:	
		STREET 1:		1896 RUTHERFORD ROAD
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92008
</SEC-HEADER>
<DOCUMENT>
<TYPE>4
<SEQUENCE>1
<FILENAME>edgar.xml
<DESCRIPTION>PRIMARY DOCUMENT
<TEXT>
<XML>
<?xml version="1.0"?>
<ownershipDocument>

    <schemaVersion>X0202</schemaVersion>

    <documentType>4</documentType>

    <periodOfReport>2005-07-01</periodOfReport>

    <issuer>
        <issuerCik>0000874015</issuerCik>
        <issuerName>ISIS PHARMACEUTICALS INC</issuerName>
        <issuerTradingSymbol>ISIS</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001181560</rptOwnerCik>
            <rptOwnerName>MUTO FREDERICK T</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>4401 EASTGATE MALL</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>SAN DIEGO</rptOwnerCity>
            <rptOwnerState>CA</rptOwnerState>
            <rptOwnerZipCode>92121</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>1</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>0</isTenPercentOwner>
            <isOther>0</isOther>
        </reportingOwnerRelationship>
    </reportingOwner>

    <derivativeTable>
        <derivativeTransaction>
            <securityTitle>
                <value>Director Stock Option (right to buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>3.95</value>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2005-07-01</value>
            </transactionDate>
            <deemedExecutionDate>
                <value>2005-07-01</value>
            </deemedExecutionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>A</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>10000</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0</value>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <value>2006-07-01</value>
                <footnoteId id="F1"/>
            </exerciseDate>
            <expirationDate>
                <value>2015-06-30</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>10000</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>10000</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value></value>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeTransaction>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">Grant of 7-1-05 to reporting person of stock options under the Isis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan.  The option vests and becomes exercisable in four equal annual installments, with the first installment vesting on 7-1-06.  The option shall be fully vested and exercisable on 7-1-09.  The option is exercisable as to 0 shares on 7-1-05.</footnote>
    </footnotes>

    <remarks></remarks>

    <ownerSignature>
        <signatureName>/s/B. Lynne Parshall, Attorney-in-Fact for Frederick T. Muto</signatureName>
        <signatureDate>2005-07-01</signatureDate>
    </ownerSignature>
</ownershipDocument>
</XML>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-24
<SEQUENCE>2
<FILENAME>mutopoa.htm
<TEXT>
<HTML><BODY><PRE>POWER OF ATTORNEY



Know all by these presents, that the undersigned hereby constitutes and appoints each of Stanley T. Crooke and B. Lynne Parshall, signing individually, the undersigned's true and lawful attorneys-in fact and agents to:

(1) execute for and on behalf of the undersigned, an officer, director or holder of 10% or more of a registered class of securities of Isis Pharmaceuticals, Inc. (Isis), Forms 3, 4 and 5 in accordance with Section 16(a) of the Securities Exchange Act of 1934, as amended (the Exchange Act) and the rules thereunder;

(2) do and perform any and all acts for and on behalf of the undersigned that may be necessary or desirable to complete and execute such Form 3, 4 or 5, complete and execute any amendment or amendments thereto, and timely file such forms or amendments with the United States Securities and Exchange Commission and any stock exchange or similar authority; and

(3) take any other action of any nature whatsoever in connection with the foregoing which, in the opinion of such attorney-in-fact, may be of benefit, in the best interest of, or legally required by, the undersigned, it being understood that the documents executed by such attorney-in-fact on behalf of the undersigned pursuant to this Power of Attorney shall be in such form and shall contain such terms and conditions as such attorney-in-fact may approve in such attorney-in-fact's discretion.

The undersigned hereby grants to each such attorney-in-fact full power and authority to do and perform any and every act and thing whatsoever requisite, necessary, or proper to be done in the exercise of any of the rights and powers herein granted, as fully to all intents and purposes as the undersigned might or could do if personally present, with full power of substitution or revocation, hereby ratifying and confirming all that such attorney-in-fact, or such attorney-in-fact's substitute or substitutes, will lawfully do or cause to be done by virtue of this power of attorney and the rights and powers herein granted.  The undersigned acknowledges that the foregoing attorneys-in-fact, in serving in such capacity at the request of the undersigned, are not assuming, nor is Isis assuming, any of the undersigned's responsibilities to comply with Section 16 of the Exchange Act.

This Power of Attorney shall remain in full force and effect until the earliest to occur of (a) the undersigned is no longer required to file Forms 3, 4 and 5 with respect to the undersigned's holdings of and transactions in securities issued by Isis, (b) revocation by the undersigned in a signed writing delivered to the foregoing attorneys-in-fact or (c) as to any attorney-in-fact individually, until such attorney-in-fact will no longer be employed by Isis.



IN WITNESS WHEREOF, the undersigned has cause this Power of Attorney to be executed as of this 4th day of December, 2002.







/s/Frederick T. Muto



</PRE></BODY></HTML>
</TEXT>
</DOCUMENT>
</SEC-DOCUMENT>
-----END PRIVACY-ENHANCED MESSAGE-----
