Objective: To research the effect and drug resistance of Duhuo Jisheng Tang on knee osteoarthritis (OA). Method: Select 113 patients met the inclusion criteria Were randomly divided into two groups. Patients in treatment group (n=56) were treated with Duhuo Jisheng Tang. Patients in control group (n=57) were treated with Glucosamine sulfate. The therapeutic course was 4 weeks in both groups. Based on Lequesne function index of OA pain evaluation of Signs and symptoms of knee joint functional activities. Result: The total effective 96.43% in treatment group,82.45% in control group, between two groups the differences were statistically significant(P<0.05),The treatment group Superior than the control group.two groups after treatment the Pain and functional index score were significantly lower, before and after treatment, the differences were statistically significant (P<0.001), The treatment group score lower than the control group, the difference was statistically significant (P<0.001).After 4 weeks of withdrawal efficacy of the control group significantly decreased (compared with the end of treatment, P<0.01), while the treatment group was not significantly lower efficacy (compared with the end of treatment, P>0.05). Conclusion: Duhuo Jisheng Tang effect of knee osteoarthritis is superior to the efficacy of Glucosamine sulfate,and has good security.