ABSTRACT: Background: Serum copeptin, the terminal part of the arginine vasopressin (AVP), is stable in plasma. The AVP is increased in diabetic patients and may play a role in the development of diabetic kidney disease. Objective: To evaluate the role of serum copeptin in the diagnosis of diabetic nephropathy in type-2 diabetes mellitus. Patients and Methods: 40 type-2 diabetes mellitus (T2DM) patients; divided into two groups, (20 with poor glycemic control, and 20 with good glycemic control), in addition to 20 non-diabetic healthy control subjects. The following investigations had been made; HbA1C, FBS, blood urea, serum creatinine and sodium, creatinine clearance (Ccr), glomerular filtration rate (eGFR), urinary protein, and urinary sodium. Serum copeptin levels were measured using an enzyme-linked immunoassay (ELISA). Results: Serum copeptin levels were significantly higher in (T2DM) patients with poor glycemic control than in (T2DM) patients with good glycemic control compared to the healthy control group. There was a significant positive correlation between serum copeptin and FBS, HbA1C, blood urea, serum creatinine, urinary Na, and 24-hour urinary protein, and a significant negative correlation with serum Na, eGFR, and creatinine clearance. The receiver operating characteristic (ROC) curve for the validity of serum copeptin, as a marker for diabetic nephropathy, at cutoff point 3452 pg/ml, showed 90% sensitivity, and 95% specificity. Conclusion: Serum copeptin is independently related to markers of kidney injury in T2DM and may be used as a marker for diabetic nephropathy. Keywords: Serum copeptin, Arginine vasopressin (AVP), Diabetic kidney disease.