Maternal malnutrition during lactation programmes for overweight and central leptin resistance in adulthood. The inhibition of lactation by maternal treatment with bromocriptine (a prolactin inhibitor) programmes for obesity, hyperleptinaemia and leptin resistance. Here, we evaluated the short- and long-term effects of early weaning (EW) on body-weight regulation, leptin signalling, and hormone and lipid profiles in rats offspring. Lactating rats were separated into two groups: EW – dams were wrapped with a bandage to interrupt the lactation in the last 3 d of lactation; control – dams whose pups had free access to milk during all lactation (21 d). Data were significant at P < 0·05. At weaning, EW pups presented lower body weight ( − 10 %), length ( − 4 %), visceral fat ( − 40 %), total fat ( − 30 %), serum leptin ( − 73 %), glycaemia ( − 10 %), serum insulin ( − 20 %) and insulin resistance index (IRI; − 30 %), but higher total body protein content (+40 %). At 180 d, EW offspring showed hyperphagia, higher length (+3 %), body weight (+8 %), visceral and total fat (+36 and 84 %), serum TAG (+96 %), glycaemia (+15 %), leptinaemia (+185 %) and IRI (+29 %); however, they showed lower total protein content ( − 23 %), leptin:body fat ratio (41 %), prolactinaemia ( − 38 %) and adiponectinaemia ( − 59 %). Despite unchanged leptin receptor (OB-R) and signal transducer and activator of transcription 3 (STAT3), they displayed lower hypothalamic janus tyrosine kinase 2, phosphorylated STAT3 and a higher suppressor of cytokine signalling 3 levels, suggesting a central leptin resistance. Adult rats that were early weaned displayed higher adiposity, insulin resistance and dyslipidaemia, which are related to metabolic syndrome development. Our model reinforces the idea that neonatal malnutrition caused by shortening of the lactation period is important for metabolic programming of future diseases.