BACKGROUND/AIMS: The mechanism by which peptide YY (PYY) stimulates colonic motility has not yet been fully elucidated. The aim of this study was to investigate PYY's mechanism of action on isolated rat colon. METHODS: An isolated rat colon was perfused with Krebs solution via the superior mesenteric artery. After a basal period, PYY was administered at concentrations of 12, 60 and 240 pM, respectively, and the intraluminal pressures were then monitored. After a pre-infusion of phentolamine, propranolol, hexamethonium, atropine, and tetrodotoxin, PYY was infused at a concentration of 240 pM and the pressures were then monitored. The contractile response was expressed as the % changes of the motility indices over the basal rates. RESULTS: The colonic motility increased significantly at the concentration of PYY of 12, 60 and 240 pM at the proximal colon (22.53+/-6.12%, 27.31+/-6.07%, and 33.93+/-8.55%, respectively) and the distal colon (6.74+/-4.45%, 37.79+/-11.53%, and 52.77+/-11.36%, respectively). PYY displayed a dose-dependent increment on distal colonic motility. The stimulatory effect of PYY was almost completely abolished by a pre-treatment with atropine, propranolol, and tetrodotoxin; However, the effect of PYY was not inhibited by hexamethonium and phentolamine. CONCLUSIONS: PYY increased the colonic motility, and the stimulatory action of PYY requires local cholinergic input via the muscarinic receptors or adrenergic input via the beta-receptors.