Increased oxidative stress and hemorheological disturbances may play very important roles in the development of microangiopathies in diabetes mellitus. This study was designed to determine the healing effect of melatonin on hemorheological parameters and diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats. Wistar male rats were divided into four groups as control, untreated-diabetic, melatonin-treated control and melatonin-treated diabetic rats. Diabetes was induced by injecting streptozotocin (45 mg/kg, i.p.). Fourteen weeks after inducement of diabetes, melatonin (10 mg/kg) was administered intraperitoneally for 5 days to the rats. Erythrocyte deformability and aggregation were measured by laser differaction analysis (LORCA). Diabetic nephropathy was assessed by histopathologic evaluation and TUNEL stain in the diabetic kidney. Decreased erythrocyte deformability and increased erythrocyte aggregation indices were determined in the diabetic group. Melatonin treatment did not improve these hemorheological abnormalities. However, renal injuries were diminished in the melatonin-treated diabetic group compared to the untreated diabetic group. Also, melatonin had an antiapoptotic effect on the diabetic kidney. It was concluded that i.p. administration of melatonin for 5 days improved renal injury in diabetic rats, probably by decreasing oxidative stress, but did not affect hemorheological changes.