OBJECTIVE: To observe therapeutic efficacy and safety of prednisone acetate combined with leflunomide in the treatment of IgA nephropathy. METHODS: 80 patients with IgA nephropathy were randomly divided into observation group and control group, with 40 cases in each group. Control group was given prednisone acetate 1.0 mg/kg, qd, 6 weeks later, decreasing gradually, decreasing to 0.5 mg/kg in 12th week; observation group was additionally given leflunomide 50 mg, qd, 3 days later decreasing to 20 mg. Both groups were given 3 months of treatment. Clinical efficacy, 24 h urinary protein quantification, Scr and BUN levels were observed in 2 groups after treatment, and ADR were recorded during treatment. RESULTS: Total effective rate of observation group (95.0%) was significantly higher than that of control group (75.0%), with statistical significance (P<0.05). After treatment, 24 h urinary protein quantification, Scr and BUN levels of observation group were significantly lower than those of control group, with statistical significance (P<0.05). The incidence of ADR in observation group (0) was significantly lower than in control group (7.5%), with statistical significance (P<0.05). CONCLUSIONS: Prednisone acetate combined with leflunomide has significant effect on IgA nephropathy, and will not increase the occurrence of ADR.