To compare efficacy of 1) Prednisone and mycophenolate mofetil (MMF) and herbal decoctions with 2) prednisone and cyclophosphamide (CYC) for treating severe IgA nephropathy. Methods:Eighty-four patients with severe IgA nephropathy were randomly given prednisone and MMF and herbal decoction (MMF group, n=42), or treated with prednisone and CYC (CYC group n=42), for 12 months. Patients were of no difference in terms of basic illness severity. In 18-month followups, observe clinical effective rate and the corresponding laboratory indicators such as 24-hour urine protein quantitative, serum creatinine, serum albumin, total protein, serum lipid levels, and adverse event. Results: 1) Effective rate: Total effective rate of MMF group was higher than that of the CYC group, 85.7% vs. 61.8% (P<0.05); 2) 24 h proteinuria in MMF group (0.6 ± 0.3) was significantly lower than that of the CYC Group (1.4 ± 0.5) (P<0.05), serum albumin and total protein (43.2 ± 4.3 and 70.2 ± 8.1) are substantially higher than those of the CYC Group (36.9 ± and 3.6 ± 7.6) (P<0.05); 3) Lipids: MMF group lipids significantly reduced after treatment, CYC groups showed no significant change (P<0.05);4) Adverse event: AE incidence of MMF Group (4.76%) was significantly lower than that of CYC Group (19%). Conclusion: Compared with prednisone and intravenous infusion of CYC therapy, Prednisone and MMF combined with TCM treatment is more effective to treat severe IgA nephropathy, reduce the 24 h urinary protein, improve serum lipids and serum albumin level, maintain renal function, and have less adverse reaction.