To investigate the pathologic change of gallbladder mucosa related to galls
tone formation, 52 mice were fed a lithogenic diet containing 1% cholestero
l and 0.5% cholic acid and we evaluated the sequential morphologic changes
in the gallbladder from two days to 40 weeks. Cholesterol gallstones began
to appear after two weeks and all the mice had gallstones after eight weeks
. At two days, the mitotic index was at its highest. The gallbladder mucosa
showed progressive hyperplastic change with earlier papillary projection o
f the folds and later inward proliferation. At the same time of stone forma
tion, mucous cells forming glands appeared. Their histochemical profile of
mucin was different from that of normal epithelium. Numbers of mucous cells
increased gradually until 24 weeks but slightly decreased afterward. These
results suggest hyperplasia and metaplasia are closely related to the gall
stone formation. Hyperplasia is probably reactive to irritating effect of l
ithogenic bile or stone. Metaplasia and cholesterol gallstone may develop s
imultaneously, and act synergistically.