OBJECTIVES: This study aims to assess the effects of systemic medical ozone (O MATERIALS AND METHODS: A total of 50 male Wistar albino rats were divided into six groups including five rats in each control and sham-operated control group and 10 rats in the remaining four groups: (i) control group, (ii) sham-operated control group, (iii) avascular necrosis group, (iv) intraperitoneal ozone given avascular necrosis group, (v) HBO therapy given avascular necrosis group, and (vi) intraperitoneal ozone and HBO given avascular necrosis group. We surgically induced osteonecrosis by cutting the ligamentum teres and placing a tight ligature around the femoral neck. At Week 11, we harvested femoral heads bilaterally from each animal and performed a macroscopic, histological evaluation and histomorphometric, immunohistochemical analysis. RESULTS: The intertrabecular mesenchymal cell ratio was substantially higher in the O CONCLUSION: The results of this experimental study suggest that the application of medical ozone alone may have a positive effect on new vessel formation and the repair process and may be more beneficial than HBO therapy and HBO+O