The expression of protein gene product 9.5 (PGP9.5), a known neuron marker, was immunohistochemically investigated in rat pancreas. In fetal pancreas, a cluster of cells expressed PGP9.5 among the initial epithelial buds at embryonic day 11.5 (E 11.5). At E 13.5, PGP9.5 appeared among elongated and branching epithelial cells as well as along nerve fibers in the mesenchyme. On E 17.5, tubular cells became ductal cells with lumen, which strongly expressed PGP9.5. In newborn rats, ductal cells of the common bile duct (CBD) to the centroacinar cells and islet cells expressed PGP9.5. Ten days after birth, the number of the ductal cells expressing PGP9.5 was reduced, and PGP9.5-negative cells appeared in half of the duct cells. On day 21, all centroacinar cells and intercalated ductal cells became PGP9.5-negative, but some CBD and interlobular ductal cells remained positive for PGP9.5. On day 28 and thereafter, PGP9.5 was no longer detected. In a pancreatic duct ligation model, acinar cells changed to cells with duct-like structure after duct ligation. These cells strongly expressed PGP9.5 on the fifth day after duct ligation. Three to four weeks after ligation, the cells with duct-like structure changed to acinar cells, islets of Langerhans and ductal cells, but the ductal cells were PGP9.5-negative at this point. These results suggested that PGP9.5 is expressed in ductal cells that possess a potential for differentiation to pancreatic endocrine cells, and therefore can serve as a marker for the progenitor of pancreatic endocrine cells.