Interleukin 1 (IL-1) plays a central role in cartilage deterioration in osteoarthritis (OA). Interleukin 1 receptor antagonist (IL-1Ra) is a natural receptor antagonist and blocks the effects of IL-1. In this study, partial disk perforation was performed bilaterally to induce an osteoarthritic joint in rabbit temporomandibular joint. Fifty micrograms of recombinant human IL-1Ra was injected into the right joint, and the contralateral joint received vehicle injection 4 weeks postoperatively. Animals were killed at different intervals. Histology and reverse transcription-polymerase chain reaction were performed for comparison. The vehicle-treated joint had typical OA-related cartilage degradation, whereas the lesions in cartilage of the IL-1Ra-treated joint were less severe than the control joint. At 12 weeks, a higher expression of aggrecan and collagen type II and a lower expression of aggrecanase were observed in the treated joint than in the control joint. At 24 weeks after injection, the expression of aggrecan and collagen type II was also higher in the treated joint than in the control joint. However, no difference in either aggrecanase or tumor necrosis factor α was found between 2 groups at 24 weeks. Our results suggest that intra-articular administration of IL-1Ra into the temporomandibular joint may be a good alternative for the treatment of cartilage degeneration in OA. There was also evidence confirming that supplemented IL-1Ra functions by modifying the signal transduction mechanisms specific to IL-1.