The effect of FK480, a cholecystokinin-A (CCK-A) selective receptor antagonist, on spontaneously developed chronic pancreatitis was examined in WBN/Kob rats. Animals at age 18 weeks (18w-Control) already had the histologic appearance of chronic pancreatitis as indicated by inflammatory cell infiltration and fibrotic degeneration with interstitial edema. Rats treated with vehicle from 18 to 26 weeks of age (26w-Control) showed further development of pancreatitis as characterized by more extensive appearance of inflammatory cell infiltration and fibrotic changes, with the pancreatic weight significantly decreased. Serum amylase levels of 26w-Control animals were slightly decreased compared with those of 18w-Control animals, although the difference was not statistically significant. When rats were treated orally with 1, 10, and 100 μg/kg FK480 from 18 to 26 weeks of age, the decrease in serum amylase levels recovered dose dependently compared with 26w-Control, and the level in animals treated with 100 μg/kg FK480 was almost the same as that in 18w-Control rats. Histologic examinations revealed that the appearance of the pancreas of animals treated with FK480 was slightly improved with respect to inflammatory cell infiltration and edematous changes at the highest dose examined, although the difference was not statistically significant. Although blockade of the CCK-A receptor could be considered to exacerbate chronic pancreatitis due to possible inhibition of the trophic action of CCK, our results suggest that CCK-A receptor antagonists may not be detrimental to chronic pancreatitis.