Introduction Serum retinol-binding protein (RBP4) is secreted by the liver and adipocytes and is implicated in systemic insulin resistance. RBP4 transports retinol and circulates in the plasma by binding to the larger transthyretin (TTR) homotetramer, forming a protein complex that reduces renal clearance of RBP4. In insulin-resistant ob/ob mice, urinary fractional excretion of RBP4 was reduced, consistent with increased retention; while TTR level is elevated (1). RBP4 is encoded by the RBP4 gene that maps to chromosome 10q23-q24 linked to increased risk for type 2 diabetes in different populations (2 - 3). Transgenic overexpression of RBP4 or injection of recombinant RBP4 in normal mice causes insulin resistance. Conversely, genetic deletion of RBP4 enhances insulin sensitivity. Increasing serum RBP4 induces hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase and impairs insulin signaling in muscle tissue (4). Expression of RBP4 is induced in adipose tissue as a consequence of decreased glucose transporter GLUT4 expression. Increased serum RBP4 is associated with insulin resistance, Type II diabetes, and metabolic syndrome such as obesity, glucose intolerance, dyslipidemia, and hypertension (5 - 6). Plasma RBP4 concentration might be a biomarker of nephropathy and cardiovascular disease in type 2 diabetic subjects (7).