Objective:To investigate the efficacy and reliability of leflunomide as a drug in the treatment of Lupus nephritis for cyclophosphamide is invailid or can not be tolerated.Methods:A total of 23 cases were observed in lupus nephritis patients determined by kidney biopsy.Before being grouped ,patients had received regular cyclophosphamide treatment because cyclophosphamide was invalid or could not be tolerated and disabled for 4 weeks.All patients at the same in the application of leflunomide combined with prednisone were observed for 6 months.During treatment a 24-hour urinary,blood routine,plasma albumin,liver and kidney function,anti-dsDNA antibody titers,complement C3,erythrocyte sedimentation rate were monitored and all side effects were recorded.Before and after treatment,We evaluated the efficacy and reliability of leflunomide and lupus activity index.Results:A total of 22 patients completed the trial,only 1 patient was out of treatment due to the cost.The patients of lupus nephritis had some responses at the second month visit and have obvious responses at the third or four month visit after therapy.The improvements were maintained at the six month.Before and after treatment ,We discovered that SLEDAI scores of all patients were significantly improved(the total effective rate was 77%.).With gastrointestinal tract symptoms,shingles,hair loss more common,the side effects of leflunomide were few and mild.Conclusions:Leflunomide combined with prednisone for cyclophosphamide was invalid or could not be tolerated in lupus nephritis had good efficacy,tolerance could be.