Objective To investigate the effect of medical ozone injection therapy on temporomandibular joint(TMJ)osteoarthritis and its pain in SD rats.Methods Fifity-four rats were randomly assigned according to a random number table into three groups:con-trol group,model group,and medical ozone group,with 18 rats in each group.In the control group,only physiological saline was in-jected during modeling;in the model group,only sodium iodoacetate was injected for modeling;in the medical ozone group,after in-jecting sodium iodoacetate into the joint cavity for modeling for one week,medical ozone was then injected into the joint cavity for inter-vention at a frequency of once a week,totaling 5 times.One week(week 2 after modeling),3 weeks(week 4 after modeling),and 5 weeks(week 6 after modeling)after medical ozone injections,6 rats from each group were euthanized.Mechanical withdrawal thresh-old of rats in each group was assessed before euthanasia,and the expression levels of interleukin-1β(IL-1β)in joint fluid of rats in each group were measured after euthanasia.Gross observation and modified Mankin's scoring were performed on TMJ cartilage of rats in each group after stained with Pelletier score and Safranin O-Fast Green.Results During the same time period,compared to the control group,the model group showed a significant decrease in the mechanical pain threshold of the TMJ in rats at 1 week,3 weeks,and 5 weeks(P＜0.01).The expression levels of IL-1β in the TMJ fluid increased(P＜0.01),and the Pelletier score and modified Mankin's score of TMJ cartilage increased(P＜0.01).In comparison to the model group,the medical ozone group exhibited a significant increase in the mechanical pain threshold of the TMJ in rats after 3 weeks and 5 weeks of medical ozone injections(P＜0.01).The expression levels of IL-1β in the TMJ fluid decreased(P＜0.01),and the Pelletier score and modified Mankin's score of TMJ cartilage decreased(P＜0.01).However,there were no statistically significant difference in the measured parameters in the TMJ cavity after 1 week of medical ozone injection(P＞0.05).Within the medical ozone group,compared to the 1-week treatment,the mechanical pain threshold of the TMJ increased(P＜0.01)and the expression levels of IL-1β in the TMJ fluid decreased at 3 weeks and 5 weeks(P＜0.01).However,there was no statistically significant difference in the Pelletier score and modified Mankin's score of TMJ cartilage(P＞0.05)between different treatment duration.Additionally,there were no statistically signif-icant differences in the mechanical pain threshold of the TMJ,expression levels of IL-1β in the TMJ fluid,Pelletier score,and modi-fied Mankin's score of TMJ cartilage between the medical ozone group at 3 weeks and 5 weeks(P＞0.05).Conclusion Medical ozone treatment for more than 3 weeks can improve temporomandibular joint osteoarthritis and its associated pain in rats.