Abstract: Objective To establish liver fibrosis model with low-dose diethylnitrosamine（DEN） in rats. Methods Thirty Wistar rats were randomly divided into model group and control group with 15 in each. The rats in the model group were treated with low-dose DEN（10 mg·kg^-1 body weight,orally,once daily） for 10 weeks. After sacrificing,the hematoxylin and eosin staining was performed to determine histopathological alterations and transmission electron microscopy（TEM） was used to observe the changes of ultrastructures in the hepatic cells. The automatic biochemical analyzer was used to measure ALT and AST levels,and biochemical methods was used to determine the content of serum SOD,MDA and GSH-Px. Results The levels of ALT and AST in the model group were（410.08±93.6） U/L and（399.7±90.9） U/L,respectively,significantly higher than those in the control group [（56.51±11.2） U/L and（63.26±10.0） U/L,P<0.001];serum contents of SOD,GSH-Px and MDA in the model group were（83.08±22.0） U/mg,（24.65±2.0） U/mg and （9.78±2.0） nmol/mg,respectively,significantly lower than those in the control group[（178.57±22.8） U/mg,（45.16±2.9） U/mg and（3.76±0.7） U/mg,P<0.01];the histological alterations of liver cells in the model group were mainly hepatic deforming,proliferation,necrosis and pseudolobule formation and the ultrastructural changes were mainly the increase of heterochromatin in the nucleus,decrease of organelle,matrix density and hepatin. Conclusion Low-dose DEN could successfully induce liver fibrosis and cirrhosis in rats with a high successful rates and stable pathological changes.

Key words: Liver fibrosis, Diethylnitrosamine, Ultrastructure, Rats