Low birth weight resulting from intra-uterine growth retardation (IUGR) is a risk factor for further development of metabolic diseases. The pig appears to reproduce nearly all of the phenotypic pathological consequences of human IUGR and is likely to be more relevant than rodents in studies of neonatal development. In the present work, we characterized the model of low birth weight piglets with particular attention to the hypothalamic leptin-sensitive system, and we tested whether postnatal leptin supplementation can reverse the precocious signs of adverse metabolic programming. Our results demonstrated that (i) IUGR piglets present altered postnatal growth and increased adiposity; (ii) IUGR piglets exhibit abnormal hypothalamic distribution of leptin receptors that may be linked to further disturbance in food-intake behaviour; (iii) postnatal leptin administration can partially reverse the IUGR phenotype by correcting growth rate, body composition and development of several organs involved in metabolic regulation. We conclude that IUGR may be characterized by altered leptin receptor distribution within the hypothalamic structures involved in metabolic regulation and that leptin supplementation can partially reverse the IUGR phenotype. These results open interesting therapeutic perspectives in physiopathology for the correction of defects observed in IUGR.