Objective To investigate the efficacy and safety of Tripterygium wilfordii Hook F (TwHF) combined with renin-angiotensin system (RAS) blockers in chronic kidney disease (CKD) stages 2~3 of IgA nephropathy. Methods 109 patients were randomized into the observation group and the control group. On the basis of taking RAS blockers, patients in the observation group received TwHF, and patients in the control group received methylprednisolone. The proteinuria, renal function and adverse effect were observed during treatment. Results At 3, 6, 9 and 12 months of treatment, proteinuria in the two groups was lower than the baseline(P <0.05). During follow-ups, there was no significant difference of eGFR between the two groups and baseline (P >0.05). Besides, there was no significant difference in terms of proteinuria, eGFR and effective rate in the two groups. The occurrence rate of adverse effects was 9.8% vs 27.4% and there was significant difference in the two groups (P < 0.05). Conclusions TwHF combined with RAS blockers can decrease proteinuria, protect renal function and have less adverse effects, and it is a useful therapeutic options for CKD stages 2 ~ 3 of IgAN.