In the continuous search for new antiinflammatory agents from natural products, dichloromethane (DCM), ethyl acetate (EtOAc) and methanol (MeOH) extracts of Ipomea fistulosa leaves were evaluated for inhibition of production of nitric oxide (NO), interleukin 1beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in lipopolysaccharide (LPS) stimulated J774A.1 cells. Among the tested extracts, the ethyl acetate (EtOAc) extract was found to be most active and activity based fractionation of this extract by column chromatography led to the identification of seven compounds for the first time from this plant. Furthermore, 3,4-dimethoxy cinnamic acid (1) exhibited two folds more potent inhibition of LPS-induced NO production (IC50 = 10.7 μg/mL) as compared with the standard, L-NAME (IC50 = 19.8 μg/mL). The present study supports the use of Ipomea fistulosa leaves for the treatment of inflammation.