Abstract: Objective To assess the clinical efficacy and safety of leflunomide (LEF) combined with methylprednisolone on idiopathic membranous nephropathy (IMN). Methods Sixty patients who were diagnosed as IMN by renal biopsy from December 2012 to December 2016 in the department of nephrology in our hospital were enrolled, and they were randomly divided into experimental group (30 cases, treated by leflunomide combined with methylprednisolone), and control group (30 cases, treated by tacrolimus combined with methylprednisolone). There was no significant difference in baseline data between the two groups on enrollment. Remission rates (complete remission and partial remission), relapse rates, remission duration, urinary protein quantitation, serum albumin levels, and creatinine levels were monitored at 4, 8 and 12 months after treatment and adverse events were assessed. Results At 4, 8 and 12 months, the complete remission rates in the experimental group and control group were 10.00% vs 13.33%, 33.33% vs 46.67% and 23.33% vs 20.00% (All P> 0.05). The remission rates (complete remission rate and partial remission rate)in two groups had no significant difference, too (53.33% vs 46.67%, 66.67% vs 56.67% and 63.33% vs 60.00%; All P> 0.05). At the 12th month, the creatinine in control group was significantly higher than that at baseline and in experimental group (P=0.029, P=0.007). Conclusion The combination of LEF and methylprednisolone is an effective and safe therapy for IMN.