PYY_3-36, released by intestinal lipid elicits functional effects that comprise the intestinal feedback response to luminal nutrients, but the pathway of action is not fully characterized. The aim of the present study was to determine the role of the apo A-IV-CCK₁R pathway in exogenous PYY_3-36 - induced activation of the gut-brain axis and inhibition of gastric emptying and food intake. PYY_3-36 (5µg/100g IP) significantly inhibited gastric emptying of a chow meal in wildtype, but not A-IV^-/- mice andCCK₁R receptor blockade with devazepide (10µg/100g), abolished PYY_3-36 -induced inhibition of gastric emptying. PYY_3-36-induced inhibition of food intake in both ad libitum fed and 16 hour fasted mice was unaltered in A-IV^-/- mice compared to wildtype controls or by CCK₁R receptor blockade with devazepide. PYY_3-36 activated neurons in the mid-region of the nucleus of the solitary tract (mid NTS; bregma -7.32 to -7.76 mm) in A-IV^+/+ mice, measured by immunohistochemical localization of Fos protein. PYY_3-36 -induced Fos expression was significantly reduced by 65% in A-IV^+/+ mice pre-treated systemically with the sensory neurotoxin capsaicin (5mg/100g), 78% by the CCK₁R antagonist, devazepide (10µg/100g), and 39% by the Y2R antagonist, BIIE0246 (200 and 600µg/100g) and decreased by 67% in apo A-IV^-/- mice compared to A-IV^+/+ controls The data suggest a role for apo A-IV and the CCK₁R in PYY_3-36-induced activation of the vagal afferent pathway and inhibition of gastric emptying, but this is likely not the pathway mediating the effects of PYY_3-36 on food intake.