The aim of this study was to investigate whether neonatal maternal separation (MS) - chronic stress experience in early life - affects the anorectic efficacy of leptin in the offspring at adolescence. Sprague-Dawley pups were separated from the dam daily for 3 h during postnatal day 1-14 or left undisturbed as non-handled controls (NH). NH and MS male pups received an intraperitoneal leptin (100 μg/kg) or saline on postnatal day (PND) 28, and then food intake and body weight gain were recorded. The hypothalamic levels of leptin-signalling-related genes, phosphorylated signal transducer and activator of transcription-3 (pSTAT3) and protein-tyrosine phosphatase 1B (PTP1B) were examined at 40 min after a single injection of leptin on PND 39 by immunohistochemistry and Western blot analysis. Leptin-induced suppressions in food intake and weight gain was observed in NH pups, but not in MS. Leptin increased pSTAT3 in the hypothalamic arcuate nucleus of NH pups, but not of MS. Interestingly, basal levels of the hypothalamic PTP1B and pSTAT3 were increased in MS pups compared with NH controls. The results suggest that neonatal MS experience may blunt the anorectic efficacy of leptin later in life, possibly in relation with increased expressions of PTP1B and/or pSTAT3 in the hypothalamus.