Background: Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction and failure of various organs. Diabetic Nephropathy (DN) is the leading cause of chronic kidney disease which ultimately progresses to end stage renal disease. Therefore, early diagnostic markers for predicting and monitoring the progression of DN are needed to enable the timely administration of the mostly appropriate protective treatments, we hypothesized that betatrophin may be a novel endocrine regulator involved in DN development. Aim of Study: It was to examine circulating betatrophin level in patients with type 2 diabetes mellitus with or without diabetic nephropathy in comparison with healthy controls. Patients and Methods: The study was carried out on forty patients with type 2 diabetes mellitus. They were recruited from internal Medicine Department of Tanta University Hospital who classified into, 20 type 2 diabetic patients without nephropathy. 20 type 2 diabetic patients with nephropathy. Another twenty apparently healthy subjects were chosen from outpatient clinics of Tanta University Hospital and served as control group. This study was carried out from June 2016 to May 2017. An approval by Ethical Committee of Tanta University Faculty of Medicine was obtained. They were subjected to thorough history taking, clinical examination including anthropometric measurements (sex, age, BMI) and laboratory investigations including glycated Hb, fasting and post prandial blood glucose, liver function tests, UACR, kidney function, lipid profile, serum betatrophin estimation by ELISA. Results: Betatrophin was significantly higher in both T 2 DM with nephropathy and T 2 DM as compared to control group and significantly higher in T 2 DM with nephropathy than T 2 DM. There was significant positive correlation between betatrophin hormone and HbA 1 c, BMI, serum total cholesterol, serum triglycerides, LDL and negative correlation with HDL in both T 2 DM group and T 2 DM with nephropathy group. There was positive correlation between betatrophin and Albumin/Creatinine Ratio (ACR) in T2DM with nephropathy group.