Objective:To observe the clinical efficacy of three-colored cream and chitosan for the treatment of knee osteoarthritis  Methods:One hundred and twenty cases with knee osteoarthritis were randomized into observation group and control group, with 60 cases in each group. Both groups were treated with articular cavity lavage therapy; simultaneously, the control group was treated with chitosan by intra-articular injection, and the observation group was treated with intra-articular injection of chitosan and external application of three-colored cream, with the course of 6 weeks  Results:The total effective rate was 93.3% in the observation group and 71.7% in the control group, with a difference between the two groups (P<0.05). After treatment, the WOMAC scores were decreased in both two groups (P<0.05), and WOMAC score of the observation group was lower than that of the control group (P<0.05)  Conclusion:Combined three-colored cream and chitosan has positive effect in improving the clinical efficiency and the function of joints for the treatment of knee osteoarthritis.