An experiment was conducted to investigate the effects of fasting and re-feeding on hypothalamic 50-AMP-activated protein kinase (AMPK) levels and (an)orexigenic neuropeptides. Male Arbor Acres chicks (7-day-old, n = 160) were allocated to four equal treatment groups: control chicks (fed ad libitum for 48 h, C48), chicks that were fasted for 48 h (F48), chicks that were first fasted for 48 h and then re-fed for 24 h (F48C24), and chicks that were fed ad libitum for 72 h (C72). Fasting for 48 h significantly (P < 0.05) increased the ratio of phosphorylated AMPKa to total AMPKa and phosphorylated LKB1 to total LKB1, whereas re-feeding for 24 h reduced these ratios to that of the ad libitum fed C72 chicks. The gene expressions of agouti-related peptide (AgRP), neuropeptide Y (NPY), melanocortin receptor 4, melaninconcentrating hormone, prepro-orexins and carnitine palmitoyltransferase-1 were significantly (P < 0.05) increased in the fasted chicks relative to the ad libitum fed C48 group. The gene expression of pro-opiomelanocortin (POMC), as well as cocaine- and amphetamine-regulated transcript (CART) was not affected by the nutritional status. Fasting significantly (P < 0.05) decreased the mRNA levels of fatty acid synthase (FAS) and sterol regulatory element binding protein-1 (SREBP-1). The results suggest that the LKB1/AMPK signal pathway is involved in the energy homeostasis of fasted chicks, and its possible role in feed intake regulation might be mediated by the AgRP/NPY rather than the POMC/CART pathway