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Objective:To screen different analogues of mangiferin pharmacologically for antipyretic activity. Methods:The naturally occurring xanthone glycoside mangiferin was isolated by column chromatography from the ethanolic extract of stem bark ofMangifera indica. Mangiferin was further converted to5-(N-phenylamino methyleno) mangiferin,5-(N-p-chlorophenylamino methyleno) mangiferin,5-(N-2-methyl phenylamino methyleno) mangiferin, 5-(N-p-methoxy phenylamino methyleno) mangiferin,5-(N, N-diphenylamino methyleno) mangiferin,5-(N-α-napthylamino methyleno) mangiferin and5-(N-4-methyl phenylamino methyleno) mangiferin analogues. The synthesized compounds were further screened for antipyretic activity along with mangiferin at a dose level of 100 and 200 mg/kg. Mangiferin and its analogues were characterized by melting point andRfvalue determination and through spectral technique likeUV, IR, and NMR spectral analysis.Results: The antipyretic activity of mangiferin as well as all analogues was found to be more significant in at higher doseie.200mg/kg which was depicted through a decrease in rectal temperature up to3 h.Conclusions:The antipyretic activity of mangiferin and its analogues may be attributed to inhibition in synthesis ofTNF-α and anti-oxidant activity associated with amelioration of inflammatory actions of cytokines.