Abstract：Objective：To observe the effect of the therapy of pricking collaterals and cupping combined with external application of Gubi San on knee osteoarthritis and its influence on cartilage tissue related signaling pathways. Methods： A total of 72 patients with knee osteoarthritis were selected as the study objects， and were divided into the observation group and the control group according to the random number table method， with 36 cases in each group. The control group was given external application of Gubi San， and the observation group was given pricking collaterals and cupping combined with external application of Gubi San，and both groups were treated for four weeks. The clinical effects in the two groups were compared， and the changes of Visual Analogue Scale (VAS)， Time Up and Go Test (TUGT)， traditional Chinese medicine (TCM) syndrome scores， maximum active range of motion (AROM)， Knee Society Score (KSS)， Western Ontario and McMaster Universities Arthritis Index (WOMAC)， and indexes of cartilage tissue related signaling pathways [interleukin-1β (IL-1β)， cyclooxygenase-2 (COX-2)] before and after treatment were compared between the two groups. Results：The total effective rate was 97.22% in the observation group， and 83.33% in the control group， the difference being significant (P＜0.05). After two weeks and four weeks of treatment， the VAS scores and TUGT levels in the two groups were decreased when compared with those before treatment (P＜0.05)； the VAS score and TUGT level in the observation group were lower than those in the control group (P＜0.05). After treatment， the TCM syndrome scores of joint pain， leg weakness and knee soreness， poor movement and difficulty in operation in the two groups were decreased when compared with those before treatment (P＜0.05)； the above four TCM syndrome scores in the observation group were lower than those in the control group (P＜ 0.05). After two weeks and four weeks of treatment，the AROM activity and KSS levels in the two groups were increased when compared with those before treatment (P＜0.05)；the AROM activity and KSS level in the observation group were higher than those in the control group (P＜0.05). After treatment，the WOMAC scores of pain，stiffness and difficulty of daily life in the two groups were decreased when compared with those before treatment (P＜0.05)， and the above three WOMAC scores in the observation group were lower than those in the control group (P＜0.05). After treatment， the IL-1β and COX-2 levels in the two groups were increased when compared with those before treatment (P＜0.05)，and the IL-1β and COX-2 levels in the observation group were higher than those in the control group (P＜0.05). Conclusion： The therapy of pricking collaterals and cupping combined with external application of Gubi San has a great curative effect on knee osteoarthritis，which can reduce the degree of joint swelling and pain，improve the knee joint activity，promote the recovery of patients' independent living ability，and effectively relieve joint pain，poor movement and other symptoms.