OBJECTIVE : To assess serum leptin in diabetic nephropathy male patients from Gaza Strip. METHODS : This case-control study comprised 132 type 2 diabetic patients and 44 non-diabetic controls. The diabetic patients were classified into three groups; 44 normoalbuminurics, 44 microalbuminurics and 44 macroalbuminurics. Data were obtained from questionnaire interview, and biochemical analysis of blood and urine samples. Patients and controls were matched for age and body mass index (BMI). RESULTS : Serum leptin was significantly higher in micro- and macro-albuminuric patients (14.6 ± 11.7 and 15.6 ± 13.5 ng/ml) than controls and normoalbuminurics (5.9 ± 4.0 and 8.1 ± 7.6 ng/ml) with P < 0.05. In general, serum glucose, urea, createnine, cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), urinary albumin and albumin creatinine ratio (ACR) were increased in diabetic groups compared to non-diabetics, and reaching their maximum increase in macroalbuminurics whereas high density lipoprotein cholesterol (HDL-C), urinary creatinine and glomerular filtration rate (GFR) were decreased reaching its maximum decrease in macroalbuminurics. Serum leptin showed significant positive correlations with diabetes duration (r = 0.188, P = 0.020), glucose (r = 0.298, P < 0.001), cholesterol (r = 0.323, P < 0.001), triglycerides (r = 0.361, P < 0.001), LDL-C (r = 0.248, P = 0.001) and urinary albumin (r = 0.256, P = 0.001) whereas negative significant correlations were found with HDL-C (r = -0.313, P < 0.001) and urinary creatinine (r = -0.202, P = 0.007). CONCLUSIONS : The comitant raise of serum leptin with urinary albumin combined with decrease in GFR makes leptin eligible candidate as a biomarker for progression towards diabetic nephropathy in type 2 diabetes.