Abstract： Objective： To observe the clinical effect of the therapy of Duhuo Jisheng tang combined with knee four needles for knee osteoarthritis of wind-cold and fixed impediment type. Methods：A total of 90 patients with knee osteoarthritis of wind- cold and fixed impediment type were divided into the observation group and the control group according to the random number table method，with 45 cases in each group. The control group was treated with glucosamine sulfate capsules orally，and the observation group was treated with Duhuo Jisheng tang orally combined with knee four needles. The clinical effects were compared between the two groups. Before and after treatment，the scores of Visual Analogue Scale (VAS)， tenderness values， scores of Western Ontario and McMaster Universities Arthritis Index (WOMAC)，Chinese medicine syndrome scores and levels of pain mediators，including 5-hydroxytryptamine (5-HT)，prostaglandin E2(PGE2)，dopamine(DA)，substance P(SP)，and inflammatory mediators，including tumor necrosis factor- α(TNF- α)，interleukin- 1(IL- 1) and interleukin- 6(IL- 6)，were compared between the two groups. Results：The total effective rate was 88.89% in the observation group，higher than that of 77.78% in the control group(P＜0.05). After treatment，the scores of VAS，WOMAC and Chinese medicine syndromes and the levels of PGE2， SP， DA， 5- HT， IL- 1， IL- 6 and TNF- α in the two groups were decreased when compared with those before treatment(P＜0.05)， and the tenderness values were increased(P＜0.05)； the scores of VAS， WOMAC and Chinese medicine syndromes and the levels of PGE2，SP，DA，5- HT，IL- 1，IL- 6 and TNF- α in the observation group were lower than those in the control group(P＜0.05)， and the tenderness value in the observation group was higher(P＜0.05). Conclusion：The therapy of Duhuo Jisheng tang combined with knee osteoarthritis of wind-cold and fixed impediment type has a good clinical effect， which can effectively alleviate the pain of patients， and its mechanism may be related to reducing the serum pain mediators and inflammatory mediators.