Abstract：Objective：To observe the clinical effect of Du Yi Wei Capsules combined with Diclofenac Sodium on osteoarthritis with blood stasis blocking collaterals syndrome. Methods： A total of 108 cases of patients with osteoarthritis with blood stasis blocking collaterals syndrome treated at Affiliated Jinhua Hospital，Zhejiang University School of Medicine from June 2021 to June 2023 were selected and divided into the control group and the observation group according to the random number table method，with 54 cases in each group. The control group was treated with Diclofenac Sodium Sustained-Release Tablets， and the observation group was additionally treated with Du Yi Wei Capsules in addition to the treatment given to the control group. Both groups were treated for two weeks continously. Clinical effects were compared between the two groups； Visual Analogue Scale（VAS） scores for pain， Western Ontario and McMaster Universities Osteoarthritis Index（WOMAC）scores for physical function，levels of inflammatory factors [matrix metalloproteinase-3（MMP-3）， interleukin-6（IL-6）， interleukin-1β（IL-1β）]， and serum pain mediators [β-endorphin（β-EP），substance P（SP），and prostaglandin E2（PGE2）] in the two groups were compared before and after treatment. Results：The total effective rate was 98.15%（53/54）in the observation group，higher than 87.04%（47/54）in the control group（P＜0.05）. The levels of MMP-3，IL-6，IL-1β，SP and PGE2，and the scores of WOMAC and VAS in the two groups were decreased when compared with those before treatment，with the observation group showing lower levels and scores than the control group（P＜0.05）. β-EP levels in the two groups were increased when compared with those before treatment（P＜0.05），with the observation group showing higher level than the control group （P＜0.05）. There was no significant difference in adverse reactions between the two groups （P＞0.05）. Conclusion：Du Yi Wei Capsules combined with Diclofenac Sodium has a good curative effect in treating osteoarthritis with blood stasis blocking collaterals syndrome. This combination can reduce inflammation responses， alleviate pain， and promote the recovery of knee joint function.