Leptin plays an important role in the regulation of body weight and energy balance. Women have higher circulating leptin level than men. In this study, we examined serum leptin concentrations in Type 2 diabetic men and women with or without nephropathy. Fasting plasma glucose (FPG), lipid profile, and serum leptin concentrations were measured in 34 Type 2 diabetic patients with nephropathy (DMN), 12 normoalbuminuric Type 2 diabetic subjects (DM) and 34 non-diabetic control subjects, all matched for age and body mass index (BMI). Result: Patients with diabetic nephropathy had lower high-density lipoprotein cholesterol and higher triglyceride, FPG, urinary albumin/creatinine ratio (ACR) and serum creatinine than the other two groups. There was a significant trend in serum leptin concentrations ( P<0.001, analysis of variance ANOVA) across the three groups with the main difference being detected between DMN and control subjects (DMN: 17.5±16.8 ng/ml, DM: 14.6±10.5 ng/ml and control: 9.1±7.1 ng/ml). Women had higher serum leptin concentration than men in the control group (12.5±7.3 ng/ml versus 4.2±2.0 ng/ml, P=0.001) and in the DM group (18.9±11 ng/ml versus 8.6±5.9 ng/ml, P=0.07) whereas this gender difference was not observed in the DMN group (18.6±17.0 ng/ml versus 16.8±17.0 ng/ml, P=0.754). On multivariate analysis, ACR ( β=0.411, P<0.001) and BMI ( β=0.240, P=0.002) were independently associated with serum leptin concentrations ( R 2=0.194, F=22.1, P<0.001) in the whole group. In the DMN group, ACR ( β=0.370, P=0.016) was the only independent determinant of serum leptin concentrations ( R 2=0.159, F=11.4, P=0.016). Serum leptin concentrations were higher in Type 2 diabetic patients with nephropathy than normoalbuminuric diabetic patients and controls. Diabetic men with nephropathy had proportionally higher serum leptin such that the gender difference in leptin observed in non-nephropathic individuals was abolished.