Background: Osteoarthritis (arthritis of the joints) is one of the most common metabolic disorders of bone tissue that reduces the process of absorption and reabsorption in bone. Exercise and stem cell injections can have beneficial effects in treating this disease. The enzymes alkaline phosphatase and osteopontin, as markers of bone formation, play an important role in diagnosing the progression or treatment of this disease. The aim of this study was to examine the effect of training, stem cells and hyaluronic acid on osteocalcin, ALP and osteopontin in the cartilage tissue of rats with osteoarthritis. Materials and Methods: In this study, 25 rats were divided in 5 groups including: (1) healthy control, (2) patient control, (3) endurance training (3 days a week for one month), (4) recipients of mesenchymal stem cells (1 × 106 cells / Kg), and (5) simultaneous recipients of endurance training and mesenchymal stem cells. Alkaline phosphatase gene expression was assessed by RT PCR and the amount of osteopontin synthesis was measured by immunohistochemistry procedure. Results: Training and mesenchymal stem cell injection had a significant effect on increasing alkaline phosphatase gene expression and osteopontin in patient rats compared to the patient control group (P <0.001). Also, simultaneous endurance training and stem cell injection have interactive effects on increasing both factors (P <0.001). Conclusion: Based on the findings of this study, it seems that endurance training and injection of mesenchymal stem cells in the joints, either separately or simultaneously, can increase the expression of alkaline phosphatase gene and the amount of osteopontin. Manuscript profile