OBJECTIVE: The aim of this study was to set up an animal model of osteoarthritis (OA) in the rabbit temporomandibular joint (TMJ). METHODS: 0.3 ml of 1.6% papain solution was injected into the upper compartment of each left TMJ of six Japanese big ear white rabbits, and the same volume of saline was injected into the upper compartment of left TMJ as control. The rabbits were sacrificed 2, 4, 6 weeks respectively after injections and the TMJ specimens were pathologically examined. RESULTS: The degenerative changes were demonstrated in the TMJs injected with papain, such as thinner articular cartilage, fibrillation and destroyed cartilage matrix, and inflammation, proliferation, and degeneration of the synovial tissue. All these changes were much worse with prolonged observation time. Some kinds of reparative changes appeared in the sixth week after papain injection. CONCLUSION: Pathological similarities between papain induced rabbit TMJ osteoarthritis and human TMJ osteoarthritis were observed. This animal model has good reproducibility and hence can be used for exploring pathogenesis of this disease and selection of treatments for osteoarthritis of TMJ.