Previous nutritional studies have shown that insulin regulation is different between DT and A strains of gibel carp. As leptin plays a pivotal role in the effects of insulin, we hypothesized that leptin regulation of glucose and lipid metabolism would differ between the two strains. To test our hypothesis, recombinant human leptin was injected into two strains. The results showed that leptin activated PI3K-AKT, AMPK-ACC, and JAK2-STAT signaling pathways in both strains. Hypoglycemia induced by leptin might be due to higher glucose uptake by the liver and muscles together with enhanced glycolytic potential and reduced gluconeogenic potential. Decreased lipogenesis and up-regulated fatty acid oxidation were induced by leptin. In terms of genotype, the PI3K-AKT signaling pathway was more strongly activated by leptin in the muscle tissue of the A strain, as reflected by the heightened phosphorylation of AKT. Furthermore, glycogen content, glycolytic enzyme activity, and gluconeogenic capability were higher in the A strain than the DT strain. Strain A had higher levels of fatty acid synthesis and lipolytic capacity in the liver than the DT strain, but the opposite was true in white muscle. Regarding leptin-genotype interactions, the DT strain displayed stronger regulation of glucose metabolism in the liver by leptin as compared to the A strain. Moreover, a more active JAK2-STAT signaling pathway accompanied by enhanced inhibition of fatty acid synthesis by leptin was observed in the DT strain. Overall, the regulation of glucose and lipid metabolism by leptin differed between the two strains, as expected.