Amylin, a peptide hormone released from pancreatic islet β-cell, exerts important anti-diabetic,anorexic, and weight-loss effects.However, the underlying cellular mechanisms and the exact action sites of amylin regulating energy balance are currently not well understood.The arcuate nucleus of the hypothalamus (ARC)plays a pivotal role in energy homeostasis.Amylin-binding and-immunoreactivity (IR) are detected in the ARC.Here we reported that amylin post-synaptically depolarized a subset of ARC neurons in a concentration-dependent manner and likely via activation of a nonselective cation channel in rat hypothalamic brain slice preparations.Subset of ARC calcitonin receptor-IR soma/terminals were co-localized or proximal appositions with pseudorabies virus (PRV)-IR after PRV injection in brown adipose tissue (BAT) of rat.Intra-ARC microinjecting amylin dose dependently increased the BAT temperature, heart rate, locomotor activity and inhibited food intake in free moving rats.These data indicate that the ARC neurons are a novel target where amylin can act to regulate energy balance.