Background: The intake of leptin during the suckling period protects against obesity and improves insulin and central leptin sensitivity in adult rats. Objective: We analyzed whether leptin treatment to neonates may also improve later peripheral leptin sensitivity in adipose tissue under high-fat (HF) diet conditions.Design: Male rats were supplemented with a daily oral dose of leptin or the vehicle (controls) during the suckling period. After weaning, animals were fed a normal-fat or an HF diet until the age of 6 months. At this age, mRNA and protein levels of the long-form leptin receptor (OB-Rb) and the expression of other genes related with energy metabolism were measured in various adipose depots (inguinal, mesenteric and retroperitoneal). Results: HF-diet feeding resulted in lower OB-Rb mRNA and protein levels in internal depots in controls but not in leptin-treated animals; these animals maintained OB-Rb mRNA and protein levels under HF-diet conditions in these depots, particularly in the mesenteric one, and this was accompanied by increased expression of genes related with energy uptake (GLUT4, CD36), fatty acid oxidation (peroxisome proliferator activated receptor-α (PPARα), CPT1, UCP3) and lipogenesis (PPARγ, GPAT). Leptin-treatment also ameliorated HF-diet-induced hepatic fat accumulation occurring in control animals. Conclusion: Leptin treatment during the suckling period may improve the lasting effects of HF-diet feeding on leptin receptor abundance in the adipose tissue and increase its oxidative capacity, resulting in a better handling and partitioning of excess fuel. This, together with the described improvement of central leptin sensitivity, may explain why these animals are more protected against diet-induced obesity and its metabolic-related disorders.