OBJECTIVE This study aims to investigate the antiinflammatory effect of tetrandrine in a rabbit model of osteoarthritis. METHODS The cruciate ligaments and medial menisci of 36 female New Zealand white rabbits (each weighing 2.0-3.0 kg) were resected. Six weeks after surgery, the animals were randomly divided into three groups (n=12 in each): tetrandrine (20 mg/kg/day), indomethacin (3 mg/kg/day) and control (saline 10 mL/day) groups. After 14 days of treatment, the results were assessed by macroscopic observation, histological evaluation, measurement of the levels of interleukin-1 beta, tumor necrosis factor-alpha and nitric oxide in the synovial fluid and messenger ribonucleic acid expression of metalloproteinase-3 in synovia. RESULTS In the tetrandrine group, the pathological changes were more attenuated than in the control group. Levels of interleukin-1 beta, tumor necrosis factor-alpha, nitric oxide and metalloproteinase-3 in the synovial fluid or synovium were all significantly suppressed in the tetrandrine group compared with the control group. There were no significant differences between the tetrandrine and indomethacin groups. CONCLUSIONS The results of this study demonstrate that tetrandrine may protect against the development of experimentally induced osteoarthritis.