Diabetes mellitus (DM) is a serious metabolic disorder with micro- and macrovascular complications that results in significant morbidity and mortality. It is well established that cytosolic Ca2+ play an important role in controlling insulin secretion in pancreatic beta-cells. The Na+/Ca2+ exchanger (NCX), an ion transport protein, is expressed in the plasma membrane of virtually all animal cells. NCX is a reversible carrier that can mediate the transport of Ca2+ across the plasma membrane in both directions. Therefore, great efforts have been made to identify NCX associated with DM. NCX is expressed in several tissues, and acts in the protection against intracellular calcium overload; in the regulation of insulin secretion by beta cells, and in improving vascular endothelium-dependent relaxation. All these mechanisms are associated with DM pathogenesis and its chronic complications. Therefore, NCX is a candidate protein for the development of these disorders. Only a few studies investigated NCX in relation to chronic complications of diabetes, with inconclusive results. (c) 2012 Elsevier Inc. All rights reserved.