Visceral and subcutaneous adipose tissue display important metabolic differences that underline the association of visceral obesity with obesity-related cardiovascular and metabolic alterations. Recently, the potential role of adipokines (visfatin and retinol binding protein-4) in the development of obesity-related insulin resistance are increasingly understood. The aim of the present study was to investigate whether plasma visfatin and retinol binding protein-4 (RBP-4) levels are correlated with obesity and type 2 diabetes mellitus and to examine their association with visceral, subcutaneous as well as fat deposition in the liver. The study was conducted on forty patients with type 2 diabetes mellitus and twenty age and sex matched healthy subjects as controls. Both diabetic and control subjects were divided into two equal groups according to the body mass index (BMI), the first was non-obese subjects with BMI < 25 Kg/ m2and the other was obese subjects with BMI ≥30 Kg/m2 (20 cases each). After full clinical evaluation, fasting plasma glucose, glycosylated hemoglobin, and lipid profile levels were estimated in all groups. Plasma visfatin, retinol binding protein-4 and serum insulin levels were measured by enzyme-linked immunosorbent assay. Insulin resistance index was calculated by the homeostasis model assessment (HOMAIR). Visceral fat, subcutaneous fat and fat deposition in the liver were measured by ultrasonography. The results of the study showed that the levels of plasma visfatin and RBP-4 were increased significantly in diabetics compared to control group; moreover, both of them were significantly higher in diabetics compared to control subjects with similar BMI values. However, Plasma visfatin concentration was positively correlated with RBP-4, BMI, waist / hip ratio (WHR), insulin, insulin resistance index and visceral fat area, while it was negatively correlated with systolic blood pressure in all diabetic patients (both obese and non-obese). On the other hand, plasma RBP-4 concentration was correlated positively with visfatin, BMI, WHR, blood glucose, insulin and insulin resistance index, and ectopic fat deposition in the liver in diabetic patients. Stepwise multiple regression analysis revealed that plasma visfatin levels remained positively correlated with visceral fat area and WHR; while plasma RBP-4 levels remained positively correlated with BMI, ectopic fat deposition in the liver and HOMAIRin all diabetic patients. Plasma visfatin levels were significantly higher in diabetics than control subjects and positively correlated with visceral fat area but not with subcutaneous fat. Although visfatin levels wereincreased in type 2 diabetes mellitus, the correlation seems to be primarily through obesity. Moreover, plasma RBP-4 levels were increased significantly in diabetics compared to control subjects. However, circulating RBP-4 is not correlated with the amount of visceral or subcutaneous fat, but, it was correlated positively with ectopic fat deposition in the liver and insulin resistance. Thus, the close relationship between circulating RBP-4 with ectopic fat deposition in the liver and insulin resistance may reflect stronger effects of RBP-4 on hepatic insulin sensitivity.