Objectives: Metabolic programming of the offspring following maternal overfeeding during gestation may be mediated by epigenetic changes in adipose tissue, the mechanisms of which remain to be elucidated. No studies have been reported on the pharmacological reversibility of such processes early in life. In this context, our aims were: (1) to study the effects of maternal overfeeding on the metabolic and epigenetic programming of adipose tissue; and (2) to test the potential of postnatal metformin treatment to reverse these changes. Methods: We studied male and female piglets born to commercial production sows (Sus scrofa domesticus) who were fed during gestation with a standard diet (control feeding piglets: CF piglets; n=16), or a hypercaloric diet (piglets from overfed sows: OF piglets; n=16). Piglets received treatment with metformin or vehicle (1:1) during lactation, and were sacrificed at weaning (28 days). At sacrifice, weight was assessed and metabolic markers in serum were analyzed: glucose, insulin, fructosamine, C-reactive protein (CRP), lipids and adiponectin. Visceral adipose tissue hypertrophy (size of the adipocytes), inflammation (gene expression of TNFA, IL6 and CCL2) and DNA methylation levels of adipogenesis genes (NDN and DLK1) were studied. Results: OF piglets showed a worse metabolic profile (higher weight, increased levels of fructosamine and CRP, and lower HOMA-β and adiponectin) together with an inflammatory phenotype in visceral adipose tissue (higher expression of CCL2) and adipocyte hypertrophy (increased area, perimeter and diameter), all p<0.05. DNA methylation analysis of adipose tissue from OF piglets disclosed a decrease in the DNA methylation levels of the adipogenesis genes DLK1 and NDN (p<0.05). Metformin treatment attenuated the metabolic alterations in adipose tissue from OF piglets, decreased hypertrophy of the adipose tissue (adipocyte area, perimeter and diameter) and increased NDN methylation levels (all p<0.05). Conclusions: Maternal overfeeding during gestation induced metabolic and epigenetic abnormalities in the adipose tissue of the offspring, and postnatal metformin treatment was found to partially reverse these abnormalities.