Experimental cholelithiasis was established by feeding hamsters with lithogenic diet. Morphological changes of extrahepatic bile ductal epithelia were observed under light and electron microscopes at weeks 1, 2, 4 and 6 after the treatment. Moreover, the changes of mucus composition in goblet cells, which were located among the epithelia, were particularly evaluated using High iron diamin-Alcian blue pH 2.5 (HID-AB) stain. Compared with the controls, goblet cells of both superior bile duct (S-BD) and inferior bile duct (I-BD) increased in number, but more prominently in I-BD than in S-BD. Furthermore, goblet cells of the controls mainly contained sulfomucin positive for the HID in their cytoplasm. On the other hand, goblet cells of the lithogenic diet group mainly contained sialomucin negative for the HID in their cytoplasm. Electron microscopy demonstrated the extensive accumulation of secretory granules in the cytoplasm of the epithelial cells of both S-BD and I-BD. These results suggest that cholelithiasis may enhance the mucus secretion from extrahepatic bile ductal epithelia, and that the mucus oversecretion results in the protective effect on biliary epithelia. On the other hand, it is suggested that the mucus oversecretion may cause the bile retention in extrahepatic bile ducts, and also may have relation to the choledochitis or pancreatitis associated with cholelithiasis.