To observe the clinical effects of Huangqi Guizhiwuwu Decoction on senile diabetic nephropathy and to analyze its effects on methylation of TGF-β gene expression regulatory region. Methods:A total of 90 cases of elderly DN patients admitted to our department from June 2016 to June 2017 were randomly divided into control group and observation group, with 45 cases in each group. Two groups of patients were under instruction of diabetes education, and took diabetes diet. Patients in the observation group took Huangqi Guizhi Wuwu Decoction on the basis of therapeutic schedule, and all the patients were treated for 3 courses (6 weeks as a course of treatment). After the treatment, clinical effects, proteinuria excretion rate and TGF-β gene methylation levels were observed. Results:1) The comparison of total effective rates of the two groups were statistically significant (P<005), and the rate in the observation group was superior to that in the control group. 2) After treatment, the uAER of the two groups was improved compared with that before treatment, and the improvement of the observation group was more significant (P<005). 3) The expressions of VEGF and mRNA in the two groups decreased after treatment, and the trend of the observation group was significantly lower than that of the control group (P<005). 4) The level of methylation of TGF-β gene was (1366±822)% in the observation group and (6689±1118)% in the control group, which was significantly lower than that in the observation group (P<005). Conclusion:Huangqi Guizhi Wuwu decoction can effectively treat senile diabetic nephropathy and its mechanism may be related to reducing the level of methylation of TGF-β gene expression regulation.