Abstract：Objective：To observe the clinical effect of Shenmai injection combined with intra-articular injection of ozone for knee osteoarthritis. Methods：A total of 110 cases of patients with knee osteoarthritis were selected and divided into the control group and the observation group according to the random number table method，55 cases in each group. The control group was given intra-articular injection of ozone，and the observation group was additionally treated with Shenmai injection based on the treatment of the control group. The clinical effect was compared between the two groups. The levels of tumor necrosis factor-α(TNF-α)，matrix metalloproteinase-1(MMP-1) and interleukin-1β(IL-1β) before and after treatment were detected in the two groups. The scores of Visual Analogue Scale(VAS)， the joint function and joint swelling degree were evaluated. Results：The total effective rate was 98.18% in the observation group，higher than that of 83.64% in the control group， the difference being significant(P＜0.05). Before treatment， compared the levels of TNF- α， MMP- 3 and IL- 1β between the two groups， there was no significance in the difference(P＞0.05). After treatment， the levels of TNF- α， MMP-3 and IL-1β in the two groups were decreased when compared with those before treatment，and the above levels in the observation group were lower than those in the control group，differences being significant(P＜0.05). Before treatment， compared the scores of VAS，the joint function and joint swelling degree between the two groups，there was no significance in the difference(P＞0.05). After treatment，the scores of VAS，the joint function and joint swelling degree in the two groups were decreased when compared with those before treatment， and the above scores in the observation group were significantly lower than those in the control group， differences being significant(P＜0.05). Conclusion： The therapy of Shenmai injection combined with intra-articular injection of ozone has significant clinical effect in treating knee osteoarthritis， which can rapidly eliminate intra- articular inflammatory reactions，relieve articular pain，reduce knee edema，and improve the activity ability of joint knee and the effective rate of treatment.