Recent studies demonstrated that cholecystokinin (CCK) at physiological levels stimulates pancreatic enzyme secretion via a capsaicin-sensitive afferent vagal pathway. This study examined whether chemical ablation of afferent vagal fibers influences pancreatic growth and secretion in rats. Method: Bilateral subdiaphragmatic vagal trunks were exposed and capsaicin solution was applied. Pancreatic wet weight, and pancreatic secretion and growth in response to endogenous and exogenous CCK were examined 7 days after capsaicin treatment. Results: Perivagal application of capsaicin increased plasma CCK levels, and significantly increased pancreatic wet weight compared with those in the control rats. Oral administration of CCK-1 receptor antagonist, loxiglumide, prevented the increase in pancreatic wet weight after capsaicin treatment. In addition, continuous intraduodenal infusion of trypsin prevented the increase in plasma CCK levels and pancreatic wet weight after capsaicin treatment. There were no significant differences in the expression levels of CCK-1 receptor mRNA and protein in the pancreas in capsaicin-treated and control rats. Intraduodenal administration of camostat or intravenous infusion of CCK-8 stimulated pancreatic secretions in control rats, but not in capsaicin-treated rats. In contrast, repeated oral administrations of camostat or intraperitoneal injections of CCK-8 significantly increased pancreatic wet weight in both capsaicin-treated and control rats. Conclusions: Present results suggest that perivagal application of capsaicin stimulates pancreatic growth via an increase in endogenous CCK, and that exogenous and endogenous CCK stimulate pancreatic growth not via vagal afferent fibers but directly in rats.