Abstract： Objective： To observe the clinical effect of the therapy of Bushen Huoxue prescription combined with diclofenac sodium on knee osteoarthritis(KOA) complicated with joint effusion. Methods： A total of 84 patients with KOA complicated with joint effusion were selected and divided into the observation group and the control group according to the random number table method，with 42 cases in each group. The control group was treated with diclofenac sodium，and the observation group was additionally treated with Bushen Huoxue prescription based on the treatment of the control group. Both groups were treated for six weeks. The clinical effects，Chinese medicine syndrome scores，pain，knee function as well as levels of interleukin-6(IL-6)，interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in synovial fluid and levels of serum osteoprotegerin(OPG)， vascular endothelial growth factor(VEGF) and matrix metalloproteinase- 3(MMP- 3) before and after treatment were compared between the two groups，and the adverse reactions were recorded. Results：The total effective rate was 92.86% in the observation group，higher than that of 73.81% in the control group(P＜0.05). After treatment，the scores of Chinese medicine syndrome and Visual Analogue Scale(VAS) as well as the levels of IL- 6，TNF- α and IL- 1β in synovial fluid in the two groups were decreased when compared with those before treatment(P＜0.05)，and the above two scores as well as the levels of IL-6，TNF-α and IL-1β in synovial fluid in the observation group were lower than those in the control group(P＜0.05)； the scores of Japanese Orthopaedic Association(JOA) in the two groups were increased when compared with those before treatment(P＜0.05)， and the JOA score in the observation group was higher than that in the control group(P＜0.05). After treatment，the serum OPG levels in the two groups were increased when compared with those before treatment(P＜0.05)，and the levels of serum VEGF and MMP- 3 were decreased(P＜0.05)；the serum OPG level in the observation group was higher than that in the control group(P＜0.05)，and the levels of serum VEGF and MMP- 3 were lower(P＜0.05). No serious adverse reactions occurred in both groups. Conclusion： The therapy of Bushen Huoxue prescription combined with diclofenac sodium for KOA complicated with joint effusion can alleviate the clinical symptoms， reduce the levels of inflammatory factors in synovial fluid，regulate the expression of serum OPG，VEGF and MMP-3，and promote the recovery of joint function with high safety.