Abstract: Objective: To investigate the effect of leucine on insulin secretion in normal rats and their isolated islets. Methods: In vitro, islets were isolated from Wistar rats by collagenase digestion. Leucine ( 0, 10, 20mmol /L) was added to low glucose ( 5.6mmol /L) /high glucose ( 25mmol /L) DMEM medium for 120min incubation with islets and the level of insulin in supernatant was measured.In vivo, 24 male Wistar rats were randomly divided into 4 groups. After overnight fasting, rats were intragastrically administered water ( Con) , 2g /kg glucose ( Glu) , 1.5g /kg leucine ( Leu) and glucose combined with leucine ( Leu + Glu) , respectively.Blood glucose and plasma insulin levels were measured at 0, 30, 60 and 120min after administration.Area under the curve ( AUC) of glucose and insulin were also calculated. Results: In vitro, 20mmol /L leucine significantly increased insulin secretion in 25mmol /L glucose medium.In vivo, leucine alone did not affect plasma levels of glucose and insulin.Comparing with Glu group, blood glucose levels at 60min and 120min significantly decreased and plasma insulin significantly increased at 30min in Glu + Leu group.Insulin AUC significantly higher in Glu + Leu group than in Glu group ( p < 0.01) and glucose AUC was significantly lower in Glu + Leu group than in Glu group ( p < 0.05) . Conclusion: Leucine increases insulin secretion in the presence of glucose, leading to the decrease of blood glucose.