Glucocorticoids (GCs) induce profound hyperphagia in birds. However, the neuronal regulatory network underlying GC-provoked hyperphagia is unclear. To determine whether any cross talk occurs among hypothalamic GC receptors (GRs), AMP-activated protein kinase (AMPK), and GCs in the regulation of appetite, we performed an intracerebroventricular injection of mifepristone (a GR inhibitor) and compound C (an AMPK inhibitor) on GC-treated male chicks. The results indicate that central GC administration increased the expression of GR and neuropeptide Y mRNA, as well as phosphorylated AMPKαThr172 and acetyl-coenzyme A carboxylaseSer79. Blocking AMPK significantly attenuated GC-induced hyperphagia. Blocking GR significantly attenuated part of the AMPK signaling pathway and GC-induced hyperphagia. Thus, the results suggest that GCs cause hyperphagia via the AMPK-neuropeptide Y signaling pathway.