Background: Total parenteral nutrition (TPN) results in the atrophy of the pancreas, while cholecystokinin (CCK) can significantly stimulate the exocrine pancreas. Aim: The present study was designed to examine if CCK may reverse the atrophy of the pancreas during total parenteral nutrition. Methods: Forty-eight Sprague-Dawley rats were orally fed or given TPN, and were infused with CCK or the CCK-receptor antagonist devazepide for 10 days. Results: Infusion of CCK caused hypercholecystokininemia (hyper CCK emia), and decreased the atrophy of pancreas resulted from TPN. The hyperplastic response to CCK in orally fed rats was decreased during TPN. Devazepide did not influence the pancreatic variables. Conclusion: CCK stimulates the pancreas, and reverses the hypotrophy of the exocrine pancreas during TPN. The trophic effect of CCK on the exocrine pancreas was declined during TPN.