ObjectiveThe aim of this study was to determine the histological and biochemical effects of high molecular weight hyaluronic acid on experimentally induced osteoarthritic changes in male rat temporomandibular joint (TMJ). DesignIn this in-vivo study, 36 male albino rats were divided into 3 groups; control non-injected, disease and treatment group. Osteoarthritis was induced using a single intra-articular injection of Complete Freund’s adjuvant (CFA) (50 μl). High molecular weight hyaluronic acid (HMWHA) was injected intra-articularly once a week, for a total of 3 injections. TMJ tissue samples were dissected from control, disease and treatment groups for biochemical analysis using ELISA test to detect the levels of matrix metalloproteinase-3 (MMP-3) on day 28. Histological examination was done using Hematoxylin &eosin, Mallory’s trichrome and Alcian blue stains. Data was analyzed using Kruskal-Wallis test followed by Dunn-Sidek method, with a 5 % significance level. ResultsTreatment group showed regaining of the normal histological features of the TMJ and decreased levels of MMP-3 when compared to disease group. ConclusionsThese findings may suggest that HMWHA plays a role in the management of CFA-induced osteoarthritic cartilage lesions.