Objective To investigate the efficacy and feasibility of combination of leflunomide and clopi-dogrel in the treatment of IgA nephropathy. Methods 84 patients with primary IgA nephropathy were randomly divided into four groups: Control group (group 1) received valsartan; test group (group 2) received valsartan +clopidogrel; group 3 received valsartan + leflunomide; group 4 received valsartan + clopidogrel + leflunomide. The level of 24 h urinary protein,serum creatinine, glomerular filtration rate and therapeutic efficacy, adverse reactions were detected and recorded during the 48 weeks follow-up. Results The 24 h urinary protein of 84 patients showed a downward trend during the course of treatment , but there were statistical differences between groups since 8 weeks after treatment (P < 0.05). The level of urine protein in group 3 and group 4 decreased significantly to 61.48% and 67.23% respectively in 48 weeks after treatment. At the end of the follow up , the serum creatinine levels in group 1 and group 2 significantly increased while the glomerular filtration rate de-creased obviously (P < 0.05). Conclusion The combination of leflunomide with clopidogrel could reduce the level of urinary proteins and slow renal function deterioration in the treatment of IgA nephropathy with less ad-verse reactions. This study provides a new idea for treatment of IgA nephropathy.