Objective To explore the main risk factors of diabetic nephropathy (DN) and to evaluate the quality of life in patients with type 2 diabetes mellitus (T2DM) in Huizhou area. Methods The data of T2DM patients who were hospitalized and revisited in XX hospital in Huizhou from January 2, 2017 to February 20, 2020 were selected, and those who met the diagnostic criteria were included in the study, and their general data were investigated and analyzed. According to the clinical data, 347 patients were divided into simple T2DM group, early DN group and clinical DN group. The differences in the clinical characteristics among the different groups were compared and the risk factors related to DN in T2DM patients were analyzed. The quality of life of patients was assessed. Results Among the 347 patients, T2DM alone accounted for 57.93%. There were 146 DN patients, accounting for 42.07% of the total. Analysis of the clinical data showed that there were significant differences in age, course of disease, waist circumference, history of hypertension, and weekly physical exercise time among the three groups (P<0.05). In addition, the differences in age, course of disease, and history of hypertension were statistically significant between the clinical DN group and other two groups (P<0.05). Age, physical exercise time less than 3h/week, and increased course of T2DM were all risk factors related to DN in T2DM patients. The quality of life of patients in the T2DM group was the highest, and the quality of life in the clinical DN group was the worst (P<0.05). Conclusion The prevalence of DN in T2DM patients in Huizhou is 42.07%. Age, physical exercise time, and course of disease are risk factors related to DN. The quality of life of DN patients is poor.