Pituitary adenylate cyclase-activating peptide (PACAP) is expressed within the gastroenteric system where it has profound physiological effects. PACAP was shown to regulate food intake and thermogenesis centrally; however, PACAP peripheral regulation of appetite and feeding behavior is unknown. Therefore, we studied PACAP's effect on appetite and food intake control by analyzing feeding behavior and metabolic hormones in PAC1 deficient (PAC1-/-) and age-matched WT mice, intraperitoneally injected with PACAP_1-38 or PACAP_1-27 prior to the dark phase of feeding. Food intake and feeding behavior were analyzed using the BioDAQ system. Active-ghrelin, glucagon-like peptide-1 (GLP-1), leptin, peptide YY (PYY), pancreatic polypeptide (PP) and insulin were measured following PACAP_1-38 administration in fasted WT mice. PACAP_1-38/PACAP_1-27 injected into WT significantly decreased in a dose-dependent manner cumulative food intake and reduced bout and meal feeding parameters. Conversely, PACAP_1-38 injected into PAC1-/-, failed to significantly change food intake. Importantly, PACAP_1-38 reduced plasma levels of active-ghrelin compared to vehicle in WT mice. In PAC1-/- mice, fasting levels of active-ghrelin, GLP-1, insulin and leptin and postprandial levels of active-ghrelin and insulin were significantly altered compared to WT. Therefore, PAC1 is a novel regulator of appetite/satiety. PACAP_1-38/PACAP_1-27 significantly reduced appetite and food intake through PAC1. In PAC1-/- mice, the regulation of anorexigenic/orexigenic hormones was abolished, while active-ghrelin remained elevated even postprandially. PACAP significantly reduced active-ghrelin in fasting conditions. These results establish a role for PACAP via PAC1 in the peripheral regulation of appetite/satiety and suggest future studies to explore a therapeutic use of PACAP or PAC1 agonists for obesity treatment.