Melatonin is a circulating hormone that is mainly re- leased from the pineal gland. It is best known as a regulator of seasonal and circadian rhythms, its levels being high during the night and low during the day. Interestingly, insulin levels are also adapted to day/night changes through melatonin-dependent synchronization. This regulation may be explained by the inhibiting action of melatonin on insulin release, which is transmitted through both the pertussis-toxin-sensitive membrane receptors MT1 and MT2 and the second messengers 3’,5’ -cyclic adenosine monophosphate, 3’,5’-cyclic guanosine monophosphate and inositol 1,4,5-trisphosphate. Melatonin may influence diabetes and associated metabolic disturbances not only by regulating insulin secretion, but also by providing protection against reactive oxygen species, since pancreatic β-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity. On the other hand, in several genetic association studies, single nucleotide polymorphysms of the human MT2 receptor have been described as being causally linked to an elevated risk of developing type 2 diabetes. This suggests that these individuals maybe more sensitive to the actions of melatonin, thereby leading to impaired insulin secretion. Therefore, block- ing the melatonin-induced inhibition of insulin secretion may be a novel therapeutic avenue for type 2 diabetes. It is best known as a regulator of seasonal and circadian rhythms, its levels being high during the night and low during the day. Interestingly, insulin levels are also adapted to day / night changes through melatonin-dependent synchronization. This regulation may be explained by the inhibiting action of melatonin on insulin release, which is transmitted through both the pertussis-toxin-sensitive membrane receptors MT1 and MT2 and the second messengers 3 ’, 5’ -cyclic adenosine monophosphate, 3 ’, 5’-cyclic guanosine monophosphate and inositol 1,4,5-trisphosphate. Melatonin may influence diabetes and associated metabolic disturbances not only by regulating insulin secretion, but also by providing protection against reactive oxygen species, since pancreatic β-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity. On the other hand, in several genetic associations tudies, single nucleotide polymorphysms of the human MT2 receptor have been described as being causally linked to an elevated risk of developing type 2 diabetes. This suggests that individuals could more more sensitive to the actions of melatonin, thereby leading to impaired insulin secretion. Therefore, block-ing the melatonin-induced inhibition of insulin secretion may be a novel therapeutic avenue for type 2 diabetes.