Abstract: Objective To observe and analyze the effects of leflunomide combined with prednisone at different doses on the clinical efficacy of IgA nephropathy, renal function and urinary proteins. Methods A total of 86 patients with IgA nephropathy who were treated in our hospital from February 2016 to February 2018 were selected as the research objects. The patients were divided into the control group and the observation group with 43 cases in each group, based on their treatment methods. Oral prednisone based on the basic therapy was received in the control group; and leflunomide combined with prednisone at different small doses, in the observation group. After treatment, clinical efficacy, renal functions and urine protein levels were compared between the two groups. Results The total clinical effectiveness rate for the control group was significantly lower than that for the observation group (P<0.05). After treatment, the levels of Scr, 24-hour urinary protein and BUN for the two groups were significantly lower than those before treatment, while the levels of eGFR were significantly increased (P<0.05). After treatment, the level of eGFR in the observation group was significantly higher than that in the control group, and the levels of Scr, 24-hour urinary protein and BUN were lower than those in the control group (P<0.05). The total incidence of adverse reactions (6.97%) for the observation group was significantly lower than that (39.3%) for the control group. Conclusions Leflunomide combined with small-dose prednisone is more clinically effective than low-dose prednisone in the treatment of IgA nephropathy. It can improve the level of renal functions, reduce 24-hour urinary protein level and increase eGFR up to the normal level in patients with IgA nephropathy to a greater extent, with certain safety. It is worthy of clinical promotion and wide application.