Abstract. The present study was undertaken to determine retinol-binding protein 4 (RBP4) levels in subjects with diabetic nephropathy. A total of 149 type 2 diabetic subjects and 19 control subjects were enrolled. Serum levels of RBP4 were measured by a method of ELISA. Serum RBP4 levels were significantly greater in the subjects with type 2 diabetes mellitus than the controls (70.5 ± 35.3 vs. 40.1 ± 13.0 µg/ml, mean ± SD, p<0.01). Serum RBP4 levels were gradually increased according to the progression of diabetic nephropathy (p value in trend test: <0.001). Its elevation was significantly greater in the diabetic subjects with stages 1, 3B and 4 than the control subjects (Stage 1: 64.6 ± 29.7, Stage 3B: 123.3 ± 71.8, Stage 4: 91.4 ± 33.8 vs. Control: 40.1 ± 13.0 µg/ml, p<0.01). Similar results were obtained in the subjects based on the amount of albuminuria (Normo-: 64.6 ± 29.7, Micro-: 63.7 ± 29.4, and Marcoalbuminuria: 90.3 ± 44.6 µg/ml, p <0.001). Serum RBP4 levels had a positive correlation with serum creatinine levels(r = 0.377, p<0.001), and a negative correlation with 1/creatinine (r = -0.420, p<0.001). Also, there was a negative correlation between serum RBP4 and the estimated glomerular filtration rate(r = -0.436, p<0.001). Multiple regression analysis showed that estimated glomerular filtration rate was an independent determinant for increased serum RBP4 levels. There was no difference in serum RBP4 levels between the advanced nephropathy with and without macrovascular diseases. These results indicate an increase in serum RBP4 levels in the type 2 diabetic subjects, particularly complicated with advanced renal impairment.