Objective To explore the effects of medical ozone on behaviors of depression model mice and its related mechanisms. Methods A total of 30 healthy male ICR mice were selected to establish depression model， and randomly divided into Sham group（ no depression treatment + normal saline）， model group（ depression treatment + normal saline）， and low， medium， and high concentration groups（ depression treatment + intraperitoneal injection of 60μg/ml， 80μg/ml and 100μg/ml medical ozone）， with six mice in each group. Depressive behaviors of mice were detected by open field experiment and behavioral despair experiment. Pathological changes in the hippocampus of mice were observed by HE staining. The levels of inflammatory cytokines of interleukin-1β（ IL-1β）， interleukin-6（ IL-6） and tumor necrosis factor-α（ TNF-α） in hippocampus of mice were detected by Western blot. Results The open field behavior experiment results of depression model mice showed that the number of horizontal crossing lattice， the number of uprights， and the number of modifications in model group were significantly less than those in Sham group（ P＜ 0.05）， and the number of defecation grains was significantly more than that in Sham group（ P＜0.05）， and the indexes in medium and high concentration groups were significantly better than those in model group（ P＜0.05）， and there were no significant differences between low concentration group and model group（ P ＞ 0.05）. The behavioral despair experiment results showed that the 4 min continuous immobility time of mice in model group after experiment was significantly longer than that in Sham group（ P ＜ 0.05）， and the time in each concentration group was significantly shorter than that in model group（ P＜0.05）. Among them， the mice in high concentration group had the largest difference. The results of body mass test showed that the body mass on the 0 d， the 7th d， the 14th d and the 21st d of mice in model group was significantly lower than that in Sham group（ P＜0.05）. On the 21st d， the body mass in high concentration group was significantly higher than that in model group（ P＜ 0.05）， and there was no significant difference in the rest of the time compared with that in model group（ P ＞ 0.05）. On the 7th d， the 14th d and the 21st d， there was no significant difference among low and medium concentration groups and model group（ P＞0.05）. The results of microscope observation showed that the number of microglia in the hippocampus of model group was significantly more than that of Sham group［ （23.64±3.57） vs（ 18.11±2.92）］（ P ＜ 0.05）， and that of high concentration group（ 17.27±2.69） was significantly less than that of model group（ P＜0.05）， and there was no significant difference among low（ 20.03±3.21） and medium （22.58±3.84） concentration groups and model group（ P＞0.05）. Western blot results showed that the levels of inflammatory factors IL-1β， IL-6， and TNF-α of hippocampus of model group were significantly higher than those of Sham group（ P ＜ 0.05）， and those of high concentration group were significantly lower than those of model group（ P＜ 0.05）， and there was no significant difference among low and medium concentration groups and model group（ P ＞ 0.05）. Conclusions High-concentration medical ozone can improve depression-like behaviors in depression model mice， and its possible related mechanism is related to the down-regulation of expression of inflammatory levels factors in brain tissue.