Objective To observe the pathological changes in the liver of p21~(HBsAg/HBsAg) transgenic mice.Methods\ The p21~(HBsAg/HBsAg) transgenic mice(2,6,12, 18,24 months) of SPF grade and corresponding p21~(+/+) mice were dissected and the livers and hepatic tumor tissues were examined by histopathology and electron microscopy.Results \ Distinct pathological changes appeared in the liver of p21~(HBsAg/HBsAg) transgenic mice both macroscopically and microscopically.With the increase of age,the liver of the transgenic mice turned to be dark and sclerotic with formation of scattered nodules and tumors.Under the light microscope,the hepatocytes were swollen and inflammatory cell infiltration occurred in the liver.Fatty degeneration appeared with punctuate,focal and crumblike necrosis.Atypical hyperplasia and hepatocellular carcinoma(HCC) developed.Resembling normal hepatocytes,the hepatpocarcinoma cells were well differentiated,forming cord-like and acinus-like structures.Under the electron microscope,the nuclei of carcinoma cells were dark stained with invagination of nuclear membrane.Mitotic figures were observed.Mitochondria were swollen with less cristae.HCC were found in four cases of 18-month-old p21~(HBsAg/HBsAg) transgenic mice(4/10,40%),and six cases of 24 months old(6/10,60%),respectively,of which metastasis occurred in two mice.Conclusions\ Prominent pathological changes occurred in the liver of p21~(HBsAg/HBsAg) transgenic mice.Well differentiated hepatocarcinoma can be developed in the mice at the age of 18 months.Metastasis of HCCs can be seen in elderly transgenic mice.