The aim of this study was to examine the association of circulating retinol binding protein 4 (RBP4) levels with β-cell function across the spectrum of glucose tolerance from normal to overt type 2 diabetes.A total of 291 subjects aged 35-60 with normal glucose tolerance (NGT), newly diagnosed impaired fasting glucose or glucose tolerance (IFG/IGT), and type 2 diabetes were screened by a standard 2-h oral glucose tolerance test (OGTT) with the use of traditional measures to evaluate β-cell function. From these participants, 74 subjects were recruited for an oral minimal model test, and β-cell function was assessed with model-derived indices. Circulating RBP4 levels were measured by a commercially available ELISA kit.Circulating RBP4 levels were significantly and inversely correlated with β-cell function indicated by the Stumvoll first-phase and second-phase insulin secretion indexes, but not with HOMA-β, calculated from the 2-h OGTT in 291 subjects across the spectrum of glycemia. The inverse association was also observed in subjects involved in the oral minimal model test with β-cell function assessed by both direct measures and model-derived measures, after adjustment for potential confounders. Moreover, RBP4 emerged as an independent factor of the disposition index-total insulin secretion.Circulating RBP4 levels are inversely and independently correlated with β-cell function across the spectrum of glycemia, providing another possible explanation of the linkage between RBP4 and the pathogenesis of type 2 diabetes.