In the present study, the anti-inflammatory effect of piperine was investigated on monosodium urate crystal-induced inflammation in mice, an experimental model for gouty arthritis, and compared it with that of the nonsteroidal anti-inflammatory drug, indomethacin. The levels of lysosomal enzymes, lipid peroxidation, tumor necrosis factor-α, and paw volume were increased significantly, and the activities of antioxidant status were in turn decreased in monosodium urate crystal-induced mice, whereas these changes were reverted to near normal levels upon piperine (30 mg/kg b.wt, i.p.) treatment. In vitro, piperine (50/100 ug/ml) suppressed the level of β-glucuronidase and lactate dehydrogenase in monosodium urate crystal-incubated polymorphonuclear leucocytes in concentration-dependent manner when compared to control cells. Thus, the present study clearly indicated that piperine inhibit the monosodium urate crystal-induced inflammation and can be regarded as therapeutic drug for the treatment of acute gouty arthritis.