Epidemiological studies provide clear evidence that mechanisms defining weight and body composition at birth impact upon obesity and insulin resistance development in latter life. The fetal programming of weight and body composition is a complex phenomenon resulting from both environmental (i.e. maternal nutrition, infections or placental conditions) and genetic factors (Ong et al. 2004; Symonds et al. 2005). Compared to Large White (commercial), Meishan (an ancient oriental breed) piglets are known to be smaller and fatter at birth. The comparison of those breeds could then represent a ‘natural’ animal model to discriminate the specific early mechanisms regulating birth weight and body composition. They could be both linked to maternal milk composition and/or fat mass transcriptional activity. Five Meishan (M) and 5 Large White (LW) sows gave birth naturally at term and the median piglet from each litter was entered into the study. Milk from sows was collected daily during the first 4 days after birth in order to measure leptin concentrations (leptin Linco, Mo, USA). Piglets were weighed daily and their total lean mass was determined by total body electrical conductivity (TOBEC) analysis. At 4 days of age they were overdosed with barbiturate. Subcutaneous adipose tissue was sampled in order to determine insulin-like growth factor I (IGF-I), IGF binding protein (IGF-BP3), peroxysome proliferator activated receptor (PPAR-gamma) and glucocorticoid receptor (GC-R) gene expressions by real-time RT-PCR. Gene expressions were assessed with the 2 – delta Ct method, taking 18S rRNA as a housekeeping gene, and expressed as relative values taken means Large White piglet values as reference (1.00). Average milk leptin was 2-fold lower (p<0.05) in the M than in the LW group. M piglets were lighter and fatter than LW piglets throughout the study (p<0.05). No significant differences were observed between the groups for IGF-I, IGF-BP3 and PPAR-gamma gene expressions. GC-R gene expressions were approximately 2.5 times higher in M than in LW subcutaneous adipose tissues (p< 0.01). GC-R gene expressions was negatively related to average milk leptin (r = -0.47; p< 0.05), total lean mass (r = -0.80; p= 0.009) and birth weight (r = -0.86; p< 0.001). Both milk composition and subcutaneous fat mass transcriptional activity differed between M and LW pig breeds. The differences in milk leptin and GC-R transcription may be supporting a stimulation of food intake and fat mass development in Meishan piglets. The comparison of these breeds could represent a useful 'natural' model to study the mechanisms programming appetite control and fat mass development.