Objective To study the clinical efficacy and safety of leflunomide combined with irbesartan in the treatment of lupus nephritis . Methods 80 cases of patients with lupus nephritis in Yueqing Hospital Affiliated to Wenzhou Medical University from May 2014 to May 2016 were selected and randomly divided into leflunomide group ( leflunomide combined with irbesartan group ) and cyclophosphamide group ( cyclophosphamide combined with irbesartan group),40 cases in each group.The urine indexes and blood indexes levels,clinical curative effect,adverse reaction of the two groups were statistically analyzed.Results The 24h urine protein,urine beta 2-MG,urine red blood cell count,blood beta beta2-MG,ESR,Cr levels of the leflunomide group were significantly lower (P<0.05),the serum albumin,C3 levels were significantly higher (P<0.05),the total treatment efficiency 97.5%was significantly higher than the cyclophosphamide group 82.5%(P<0.05),the incidence of adverse reactions 5.0%was significantly lower than the cyclophosphamide group 22.5%(P<0.05).Conclusion Leflunomide combined with irbesartan is safe and effective in the treatment of lupus nephritis.