OBJECTIVE： To observe the efficacy and safety of cyclophosphamide， leflunomide sequentially combined with prednisone in the treatment of membranous nephropathy in stage Ⅱ. METHODS： 72 patients with membranous nephropathy in stage Ⅱ were randomly divided into group A（24 cases）， B（24 cases） and C（24 cases）. All patients were given angiotensin converting enzyme inhibitor （ACEI） Benazepril hydrochloride tablet， warfarin， dipyridamole， calcium and other conventional treatment. Based on it， group A was orally given 50 mg Compound cyclophosphamide tablet， twice a day， for continuous 3 months+1.0 mg/（kg·d） Prednisone tablet， it was reduced 5 mg every 2 weeks after 2 months， then it reduced 2.5 mg every 2 weeks when 30 mg/day， and then it maintained 4-6 months when 10 mg/day， it lasted for 12 months. Group B was given 50 mg Leflunomide tablet， it changed as 20 mg/day after 2 d， and for continuous 6 months+Prednisone tablet （the same dosage and usage as group A）. Group C was given Compound cyclophosphamide tablet （the same dosage and usage as group A） was orally given in 1-3 months， and Leflunomide tablet （the same dosage and usage as group B） in 4-9 months Prednisone tablet （the same dosage and usage as group A）. Clinical efficacy， 24 h urinary protein， albumin， total cholesterol， serum creatinine， alanine aminotransferase before and after 3， 6， 9 and 12 months and incidence of adverse reactions in all groups were observed. RESULTS： Before treatment， there were no significant differences in the 24 h urinary protein， albumin， total cholesterol， serum creatinine and alanine aminotransferase among all groups （P＞0.05）. After treatment， 24 h urinary protein， total cholesterol， serum creatinine and alanine aminotransferase in all groups were significantly lower than before， and they gradually decreased by treatment time， 24 h urinary protein in group C was lower than group A and B， albumin was significantly higher than before and gradually increased by treatment time， and group C was higher than group A and B， the differences were statistically significant （P＜0.05 or P＜0.01）； but there was no significant difference between group A and B （P＞0.05）. The total effective rate in group C was significantly higher than group A and B， the difference was statistically significant （P＜0.05）， but there was no significant difference between group A and B （P＞0.05）. And there was no significant difference in the incidence of adverse reactions among 3 groups （P＞0.05）. CONCLUSIONS： Based on the conventional treatment， the efficacy of cyclophosphamide， leflunomide sequentially combined with glucocorticoid is superior to cyclophosphamide or leflunomide alone in the treatment of membranous nephropathy in stage Ⅱ， with similar safety.