OBJECTIVE： To explore the efficacy and safety of leflunomide combined with prednison in the treatment of membranous nephropathy. METHODS： 43 patients with primary membranous nephropathy were randomly divided into control group （21 cases） and test group （22 cases）. Control group given cyclophosphamide interrupted shocks combined with prednison， test group received leflunomide combined with prednison， the treatment course for both groups was 12 months. 6 months after the treatment， clinical efficacy， changes in renal function and serum lipids indexes before and after treatment， and the incidence of adverse reactions in 2 groups were observed. RESULTS： The total effective rate in test group was 63.64％， which was significantly higher than control group （23.81％）， the difference was statistically significant （P＜0.05）. After treatment， urine protein in 2 groups significantly decreased， plasma albumin significantly increased， serum creatinine， serum cholesterol， triglycerides and low-density lipoprotein significantly decreased， the differences were statistically significant （P＜0.05）； and the changes of above-mentioned indexes （except blood cholesterol） in test group were more significantly than control group， the differences were statistically significant （P＜0.05）. The incidence of adverse reactions in test group was 9.09％， control group was 9.52％， there was no significant difference between 2 groups （P＞0.05）. CONCLUSIONS： Compared with cyclophosphamide interrupted shocks combined with prednison， the efficacy of leflunomide combined with prednison in the treatment of membranous nephropathy is more definite， and the improvement of renal function and serum lipids indexes is more obvious.