Objective To observe the therapeutic effects of probucol combined with epalrestat in the treatment of early diabetic nephropathy (DN). Methods A total of 55 cases of early DN admitted in Zhongguancun Hospital from January 2014 to January 2016 were recruited in this study. They were divided randomly into 2 groups, the treatment group (50 mg epalrestat, tid and 0.5 g probucol, bid) and the control group (only 0.5 g probucol, bid). The 2 groups of patients were given diabetic diet with low protein, and kept well control of blood glucose and blood pressure. The 2 groups were treated for 24 weeks and some indicators were measured to evaluate the therapeutic results. Results The serum levels of creatinine (SCr), hyper-sensitivity C-reactive protein (hs-CRP) and urinary albumin excretion rate (UAER) were all reduced in the both groups after the treatment (P<0.05). The above indicators were decreased more significantly in the treatment group than in the control group (P<0.05). Conclusion Probucol combined with epalrestat is superior to single use of probucol in decrease of proteinuria in the patients with early DN.