The aim of this study was to determine the efficacy of Hylan G-F 20 on experimentally induced osteoarthritic changes in rabbit temporomandibular joint (TMJ). A 3 mg/ml concentration of sodium mono iodoacetate (MIA) had been injected into both joints of 24 rabbits to create osteoartrosis. The study group was injected with Hylan G-F 20 in one joint and saline in the contralateral joint as a control (once a week for 3 weeks). Histological changes in articular cartilage, osteochondral junction, chondrocyte appearance and subchondral bone were determined at 4, 6, and 8 weeks. Regarding cartilage, there was a statistically significant difference between the two groups at 4 weeks. Degenerative bony changes to subchondral bone were significantly higher in the controls. No statistical difference was found in the study group at 6 weeks. A positive correlation was found between osteochondral junction and subchondral bone in the study group at 8 weeks. The changes in chondrocyte appearance were significantly decreased in the study group at all follow-up times. Intra-articular injection of Hylan G-F 20 decreased cartilage changes in early stage TMJ osteoartrosis and clustering of chondrocytes showed the chondroprotective effects of Hylan G-F 20 caused by hypertrophic responses.