Objective To investigate correlation between serum bilirubin levels of different subtypes and diabetic nephropathy(DN)in patients with type 2 diabetes mellitus(T2DM).Methods Clinical data of 494 patients with T2DM admitted to Suizhou Central Hospital Affiliated to Hubei Medical University from January 2019 to May 2023 were retrospectively analyzed,and they were divided into DN group(175 cases)and non-DN group(319 cases)according to whether they had DN.Correlation between levels of total bilirubin(TBil),direct bilirubin(DBil),indirect bilirubin(IBil)in serum and the occurrence of DN were analyzed.Results There were statistically significant differences on age,course of diabetes,hypertension,coronary heart disease,smoking,drinking,TBil,DBil,IBil,alanine aminotransferase(ALT),blood urea nitrogen(BUN),serum creatinine(SCr),uric acid(UA),total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL),high density lipoprotein(HDL),glycosylated hemoglobin(HbA1c),body mass index(BMI),systolic blood pressure,fasting plasma glucose(FPG)and estimated glomerular filtration rate between two groups.Age,course of diabetes,hypertension,coronary heart disease,TBil,DBil,IBil,ALT,BUN,SCr,UA,TC,TG,HDL,LDL,HbA1c,BMI and FPG were influencing factors of DN in female T2DM patients(P<0.05).Age,course of diabetes,hypertension,coronary heart disease,smoking,alcohol consumption,TBil,DBil,IBil,ALT,BUN,SCr,UA,TC,TG,HDL,LDL,HbA1c,BMI and FPG were influencing factors of DN in male T2DM patients(P<0.05).TBil,DBil and IBil were significantly correlated with development of DN in patients with T2DM(P<0.001).Risk of developing DN gradually decreased with increasied TBil(1-15 μmol/L),IBil(1-10 μmol/L)and DBil(1-4 μmol/L),but after TBil>15 μmol/L,IBil>10 μmol/L and DBil>4 μmol/L,increased in TBil,DBil and IBil levels no longer reduced risk of developing DN.Conclusion There is a non-linear correlation between levels of TBil,DBil,IBil and risk of DN in patients with T2DM.Within a certain range,TBil,DBil and IBil are independent protective factors for occurrence of DN,and reaching a certain level will no longer reduce risk of DN.There is no significant difference between serum bilirubin and risk of DN in different genders.