Abstract: Carbohydrates (CHO) play serve as primary energy and carbon sources for animals and are therefore widely used incorporated into practical feeds. However, unlike mammals, teleosts are generally considered unable to utilize carbohydrates efficiently, most species are "glucose intolerant" and often exhibit prolonged post-prandial hyperglycemia after glucose loading or carbohydrate-rich meals. The underlying mechanisms remain poorly understood. Leucine, a branched-chain essential amino acid required for optimal growth in mammals and fish, improves glucose tolerance and insulin sensitivity, yet the long-term effects of leucine supplementation on growth and intermediary metabolism in fish fed high-carbohydrate diets have not been examined. In this study, a 12-week feeding trial was performed to fish body weight (5.35 ± 0.04) g were randomly fed three diets, namely CON group (10% carbohydrate level), high-carbohydrate group (HC, 20% carbohydrate level), high carbohydrate + leu group (HCL, 20% carbohydrate level + 2.0% leucine). The results showed that fish fed the HC diet had a lower final fish weight, specific growth rate (SGR), weight gain rate (WGR), feed coefficient (FCR), as well as the expression of g6pase, pparα, cptIa and aco1 compared to those fed the CON diets, whereas plasma glucose, triglyceride (TG), advanced glycation end products (AGES) and glycosylated serum protein (GSP) levels, liver lipid content, as well as the expression of glut2, gk, pk, gs, srebp1, fas, acc1, chrebp and selp showed an opposite trend. FCR, the plasma glucose, AGES and GSP levels, liver lipid content, as well as the expression of foxo1, fbpase, and g6pase of HCL groups were significantly (P < 0.05) decrease compared to those of the HC groups, whereas the opposite was true for final fish weight, SGR and WGR, whole body lipid contents, as well as the expression of glut2, gk, pk, gs, srebp1, fas, acc1, chrebp, selp, pparα, cptIa and aco1. Overall, leucine could improve the growth performance and feed utilization of M. salmoides fed the high-carbohydrate feed through the stimulation of glycolysis, glycogenesis, lipogenesis and fatty acid oxidation coupled with the depression of gluconeogenesis. These findings advance our understanding of how leucine modulates carbohydrate metabolism in fish.