Background: Osteoarthritis (OA) is one of the most common progressive diseases in the joints. A few studies have evaluated the effect of combined endurance training (ET), hyaluronic acid (HA), and mesenchymal stem cells (MSCs) on bone mass. Objectives: The present study aimed to examine the effect of ET, HA, and MSCs on osteocalcin (OC) gene expression in cartilage tissues of rats with knee OA. Methods: In this experimental study, 40 rats with OA were divided into eight groups of five rats, including (1) control, (2) MSCs, (3) HA, (4) ET, (5) HA + MSCs, (6) ET + HA, (7) ET + MSCs, and (8) ET + MSCs + HA. To investigate the effects of OA on OC, five rats were assigned to the healthy group. During eight weeks, the ET groups ran on a treadmill three sessions per week (30-50 min at a speed of 16 m/min), the MSC groups received MSCs (1 106 cells/kg) intra-articularly, and the HA groups were treated with a 10 mg/mL intra-articular therapeutic dose of HA. The OC gene expression levels were measured by the real-time PCR method. The Shapiro-Wilk and one-way ANOVA with Tukey’ s post hoc tests were used to analyze the data (P 0. 05). Results: Osteoarthritis significantly decreased OC (P 0. 05); nevertheless, ET + HA + MSCs, HA + MSCs, ET + HA, and ET + MSCs significantly increased OC (P 0. 05). Also, OC was significantly higher in the ET + HA + MSCs group than in either of ET, HA, or MSC groups (P 0. 05). Conclusions: It seems that a combination of ET, HA, and MSCs has more favorable effects than each one alone on the improvement of OC in cartilage tissues of rats with knee OA.