The effect of oral administration of protease inhibitor (camostat) on pancreatic morphology and exocrine function (conscious rat model) was investigated using WBN/Kob rats with spontaneous chronic pancreatitis. In nontreated WBN/Kob rats (2-12 months of age), pancreatic fibrosis and parenchymal destruction compatible with human chronic pancreatitis appeared at 3 months and advanced with each month. Pancreatic secretion was markedly impaired at all ages. In WBN/Kob rats fed diets containing camostat (from 2-3 or 4-5 months of age), the pancreas was hypertrophic and did not show any histological appearances compatible with chronic pancreatitis, and moreover, exocrine function was thoroughly restored with increased plasma cholecystokinin concentrations. Oral administration of protease inhibitor has both preventive and therapeutic effects on pancreatic lesions and dysfunction in an animal model of chronic pancreatitis, probably via endogenous cholecystokinin release.