<SUBMISSION>
<ACCESSION-NUMBER>0000874015-05-000001
<TYPE>4
<PUBLIC-DOCUMENT-COUNT>1
<PERIOD>20050103
<FILING-DATE>20050104
<DATE-OF-FILING-DATE-CHANGE>20050104
<REPORTING-OWNER>
<OWNER-DATA>
<CONFORMED-NAME>LOWENSTAM PATRICIA
<CIK>0001073386
<STATE-OF-INCORPORATION>DE
<FISCAL-YEAR-END>1231
</OWNER-DATA>
<FILING-VALUES>
<FORM-TYPE>4
<ACT>34
<FILE-NUMBER>000-19125
<FILM-NUMBER>05509183
</FILING-VALUES>
<BUSINESS-ADDRESS>
<PHONE>760-6032460
</BUSINESS-ADDRESS>
<MAIL-ADDRESS>
<STREET1>2292 FARADAY AVE
<CITY>CARLSBAD
<STATE>CA
<ZIP>92008
</MAIL-ADDRESS>
</REPORTING-OWNER>
<ISSUER>
<COMPANY-DATA>
<CONFORMED-NAME>ISIS PHARMACEUTICALS INC
<CIK>0000874015
<ASSIGNED-SIC>2834
<IRS-NUMBER>330336973
<STATE-OF-INCORPORATION>DE
<FISCAL-YEAR-END>1231
</COMPANY-DATA>
<BUSINESS-ADDRESS>
<STREET1>2292 FARADAY AVE
<CITY>CARLSBAD
<STATE>CA
<ZIP>92008
<PHONE>7609319200
</BUSINESS-ADDRESS>
<MAIL-ADDRESS>
<STREET1>2292 FARADAY AVE
<CITY>CARLSBAD
<STATE>CA
<ZIP>92008
</MAIL-ADDRESS>
</ISSUER>
<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>2005-01-03</periodOfReport>

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

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001073386</rptOwnerCik>
            <rptOwnerName>LOWENSTAM PATRICIA</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>2292 FARADAY AVENUE</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>CARLSBAD</rptOwnerCity>
            <rptOwnerState>CA</rptOwnerState>
            <rptOwnerZipCode>92008</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>0</isDirector>
            <isOfficer>1</isOfficer>
            <isTenPercentOwner>0</isTenPercentOwner>
            <isOther>0</isOther>
            <officerTitle>Vice President</officerTitle>
        </reportingOwnerRelationship>
    </reportingOwner>

    <derivativeTable>
        <derivativeTransaction>
            <securityTitle>
                <value>Employee Stock Option (right to buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>5.80</value>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2005-01-03</value>
            </transactionDate>
            <deemedExecutionDate>
                <value>2005-01-03</value>
            </deemedExecutionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>A</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>18158</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0</value>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <value>2009-01-03</value>
                <footnoteId id="F1"/>
            </exerciseDate>
            <expirationDate>
                <value>2012-01-02</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>18158</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>18158</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value></value>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeTransaction>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">Grant of 1-3-05 to reporting person of stock options under the Isis Pharmaceuticals, Inc. 1989 Stock Option Plan.  25% of the shares subject to the option will vest and become exercisable on 1-3-06.  Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 4,540 shares per year for the first two years, then 4,539 shares for the remaining two years.  The option is exercisable as to 0 shares on 1-3-05.</footnote>
    </footnotes>

    <remarks></remarks>

    <ownerSignature>
        <signatureName>B. Lynne Parshall, Attorney-In-Fact, for Patricia Lowenstam</signatureName>
        <signatureDate>2005-01-04</signatureDate>
    </ownerSignature>
</ownershipDocument>

</XML>
</TEXT>
</DOCUMENT>
</SUBMISSION>
