The effect of melatonin (100 µg/ml) on basal and glucose-induced insulin secretion was investigated using micro-dissected pancreatic islets of obese hyper-glycaemic mice and their normal lean littermates, and pieces of rat pancreas. Melatonin had no significant effect on basal insulin secretion from both normal and obese mouse islets, but significantly reduced basal insulin secretion from pieces of rat pancreas. However, glucose-induced insulin secretion was significantly inhibited by melatonin in both preparations. A constant infusion of melatonin into rats undergoing intravenous glucose tolerance tests did not alter blood sugar levels and produced only a marginal decrease in plasma insulin levels. It is suggested that melatonin may be involved in the monoaminergic regulation of insulin secretion