Retinol-binding protein 4 (RBP4) has been reported to be involved in the development of insulin resistance and diabetes. This study was designed to investigate serum levels of RBP4 in patients with type 2 diabetes with and without diabetic retinopathy. Based on ophthalmological examination, 92 patients with type 2 diabetes were divided into three subgroups: those without diabetic retinopathy (NDR; n = 40); those with simple diabetic retinopathy (SDR; n = 37); and those with proliferative diabetic retinopathy (PDR; n = 15). The serum RBP4 level was significantly elevated in individuals with PDR compared with those with NDR or SDR. There was a significant positive correlation between serum RBP4 level and the urine albumin excretion rate (r = 0.219). This study showed that RBP4 may be involved in the process of diabetic retinopathy and may be a novel biomarker for its diagnosis and treatment in diabetic patients.