Introduction: The aim of the research was to investigate the effect of 8 weeks’ exercise training and ozone therapy on articular cartilage tissue mRNA Beclin-1, AMPK, and mTOR gene expression in rat’ s model of osteoarthritis (OA). Materials and Methods: In this experimental study, 40 adult male rats 210± 10 gr were randomly divided into 5 groups: 1) control (CN), 2) OA, 3) OA + ozone, 4) OA + exercise training and 5) OA + ozone + exercise training groups. The knee OA was induced by the surgical method in rats. The exercise training included running on a treadmill for 8 weeks, five times a week, and 35-45 minutes in an exercise session and with 18m per minute speed. Rats in the ozone group received ozone (O3) at a concentration of 20μ g/ml, once weekly for 3 weeks. 48 hours after the programs and fasting, cartilage tissues were isolated, and articular cartilage tissue mRNA Beclin-1, AMPK, and mTOR gene expression were considered using Real-Time PCR (RTPCR). Results: In cartilage tissue, Beclin-1levels had a significant decrease in the OA group, but AMPK and mTOR levels increase. Ozone, exercise training, and ozone + exercise training Caused to reverse the process (P=0. 009). But, there was no significant difference between these groups (P≥ 0. 05). Conclusion: According to the results of this study, ozone therapy and moderate-intensity exercise training Increase Beclin-1levels in the articular cartilage tissue. However, moderate-intensity exercise training with adjustable levels of mTOR may Play a greater role in the control of articular chondrocyte autophagy in rat’ s model of OA.