Insulin and glucagon are the main hormones involved in the regulation of glycaemia, their impaired secretion is a hallmark of type I and type II diabetic individuals. Additionally, insulin is involved in lipogenesis and weight gain, provoking an anorexigenic action. The endocannabinoid system contributes to the physiological regulation of energy balance, food intake and lipid and glucose metabolisms. Despite that, an experimental link between the endocannabinoid system and the endocrine pancreas has not yet been described. Using quantitative real time PCR and immunocytochemistry we have demonstrated the existence of both CB1 and CB2 receptors in the endocrine pancreas. While the CB1 receptor is mainly expressed in non-beta cells, the CB2 type exists in alpha- and beta- cells within the islet. The endocannabinoid 2-arachidonylglycerol (2-AG) through CB2 receptors regulates [Ca²⁺]_i signals in beta-cells and as a consequence it decreases insulin secretion. In alpha-cells it regulates low glucose induced [Ca²⁺]_i oscillations. These effects may be a new component involved in the orexigenic effect of endocannabinoids and constitutes a potential target for pharmacologic manipulation of the energy balance.