Background: Diabetic nephropathy is one of the most dangerous complications of diabetes mellitus. To prevent these complications in diabetic patients monitoring of patients is a must. In last decades many authors were trying to investigate molecular biomarker to detect patients who are at risk. MicroRNA-377 is one of the promising biomarkers for prediction of diabetic nephropathy. Objective: This study aimed to investigate the role of miRNA-377 as early predictor of diabetic nephropathy in patients with type 2 diabetes mellitus. Patients and methods: Seventy five patients with type 2 diabetes and 25 healthy control participants are enrolled in a case-control study. Clinical evaluation, and laboratory investigations including fasting plasma glucose, serum creatinine, fasting lipid profile, glycosylated hemoglobin, estimated glomerular filtration rate (eGFR) and albumin creatinine ratio, The expression of serum miRNA-377 was measured via quantitative real-time-polymerase chain reaction (qRT-PCR). Results: Expression of miR‑377 could differentiate diabetic patients from healthy control as the expression of miR-377 was significantly higher in overall T2DM patients than in the healthy control (2.5 fold change, P<0.001), and was progressively increased in the normoalbuminuric group and further increased in the microalbuminuric and macroalbuminuric groups (1.92, 2.76, 3.38 fold change respectively, P<0.001). MiR-377 expression levels were positively correlated with diabetes duration, fasting plasma glucose, HbA1_C, total cholesterol, LDL-C, triglycerides, creatinine and ACR, while miR-377 expression levels were significantly negatively correlated with HDL-C and eGFR. Conclusions: MiR-377 might act as a promising biomarker for prediction of development of diabetic nephropathy in type 2 diabetes patients.