Melatonin referred as the hormone of darkness is mainly secreted by pineal gland, its levels being elevated during night and low during the day. The effects of melatonin on insulin secretion are mediated through the melatonin receptors (MT1 and MT2). It decreases insulin secretion by inhibiting cAMP and cGMP pathways but activates the phospholipaseC/IP3 pathway, which mobilizes Ca2+from organelles and, consequently increases insulin secretion. Both in vivo and in vitro, insulin secretion by the pancreatic islets in a circadian manner, is due to the melatonin action on the melatonin receptors inducing a phase shift in the cells. Melatonin may be involved in the genesis of diabetes as a reduction in melatonin levels and a functional interrelationship between melatonin and insulin was observed in diabetic patients. Evidences from experimental studies proved that melatonin induces production of insulin growth factor and promotes insulin receptor tyrosine phosphorylation. The disturbance of internal circadian system induces glucose intolerance and insulin resistance, which could be restored by melatonin supplementation. Therefore, the presence of melatonin receptors on human pancreatic islets may have an impact on pharmacotherapy of type 2 diabetes.