In the neonate, plasma leptin peaks one week after birth and both acute and chronic exogenous administration promotes the loss of the brown adipose tissue (BAT) specific uncoupling protein (UCP)-1 (Mostyn et al. 2001). Recently, increased proinflammatory pathways and macrophage numbers in adipose tissue have been implicated in the metabolic complications of obesity (Weisberg SP et al. 2003). UCP2, another inner mitochondrial protein, is genetically linked to obesity and type 2 diabetes, and has been implicated in macrophage-mediated immunity (Arsenijevic D et al. 2000). The effect of acute and chronic leptin administration on UCP2 and glucocorticoid receptor (GCR) mRNA abundance in neonatal BAT has not been determined. For the acute study, 7 pairs of 1-day old, triplet lambs received sequentially 10, 100 and 100ug leptin (L) or vehicle (V), before humane euthanasia 4 hours from start of the study and BAT sampling. While in the chronic study, 9 pairs of 1-day old lambs received either 100ug L or V daily for 6 days, before humane euthanasia and BAT sampling on day 7. All procedures were carried out according to UK animal legislation. BAT total RNA was isolated and mRNA abundance was measured by RT-PCR using oligonucleotide primers designed specifically to ovine UCP2 and GCR. Results are given as means (±SEM) relative to 18S rRNA. Statistical differences between groups were analysed by Mann-Whitney U test. Lamb body and BAT weights, and BAT per kg body weight were similar between groups and increased appropriately with postnatal age. Acute leptin administration decreased both UCP2 (V 96.7±5.1, L 73.3±5.0, p<0.05) and GCR (V 72.7±1.4, L 44.3±2.7, p<0.05) mRNA abundance, while this pattern was reversed with chronic leptin administration (UCP2: V 73.8±5.3, L 97.0±6.4, p<0.05; GCR: V 53.4±4.1, L 67.8±3.3, p<0.05). Overall, there was a positive correlation between UCP2 and GCR mRNA (Spearman′s Rank Order Test R=0.62, p<0.0001). In conclusion, acute and chronic administration of leptin had differential effects on UCP2 and GCR mRNA abundance in neonatal BAT. In particular, the chronic leptin effects may be important in promoting adipose tissue inflammation and subsequent excess growth of fat.