Objective: The aim of this experimental study was to evaluate and compare the chondroprotective efficacy of intra-articular hyaluronic acid, tenoxicam and vitamin E in osteoarthritis. Methods: An osteoarthritis model was created by anterior cruciate ligament transection and medial menisectomy in knees of 28 rats. The rats were randomized into four groups; first group served as a control group and received intra-articular injections of saline solution, intra-articular HA, intra-articular tenoxicam and intra-articular Vit E were applied to the treatment groups. First intra-articular injections were applied at second week postoperatively and repeated once a week for 5 weeks. At 8th week after the operation groups were compared based on the histologic scores of cartilage degeneration by Mankin Histological Grading Scale. Results: Total cartilage degeneration score was significantly increased in the control group (P=0.004). Total Mankin scores of HA, tenoxicam and Vit E groups were significantly lower than the control group (P=0.004, P=0.016, P=0.012 respectively). There was no statistically siginificant difference between the treatment groups in terms of total Mankin scores (P>0.05). Conclusion: Intra-articular application of HA, tenoxicam and Vit E are chondroprotective in early osteoarthritis model in rats. Chondroprotective activity of tenoxicam and Vit E are comparable with the beneficial effects of HA on articular cartilage.