Objective：To compare the differences between two mouse models of cholestatic liver injury induced by bile duct ligation （BDL）and α-naphthylisothiocyanate（ANIT）respectively，and to explore the applicability of these models in cholestatic liver injury research. Methods：Male C57BL/6 mice were randomly divided into six groups：control，sham，BDL，BDL + short - chain fatty acid （SCFA），ANIT，and ANIT+ SCFA groups. BDL and BDL+ SCFA groups underwent BDL surgery on day 1，while ANIT and ANIT+ SCFA groups were administered 100 mg/kg ANIT via gavage weekly starting from day 1 to induce liver injury，BDL+SCFA and ANIT+ SCFA groups received water containing SCFA（67.5 mmol/L sodium acetate，25.9 mmol/L sodium propionate，and 40 mmol/L sodium butyrate）for 14 days. After the collection of liver tissues and serum samples from mice of each group，liver histopathology was assessed by hematoxylin and eosin（HE）staining. Serum levels of alanine aminotransferase（ALT），aspartate aminotransferase（AST），alkaline phosphatase（ALP），and total bilirubin（TBIL）were measured using biochemical assay kits，while the concentrations of inflammatory cytokines interleukin（IL）-6，IL-1β，and monocyte chemoattractant protein-1（MCP-1）were determined by ELISA. Results：Mice in the BDL group exhibited marked jaundice and continuous weight loss within the first week，progressing to severe jaundice by the second week. In contrast，the ANIT group displayed mild jaundice in the early stage，which gradually worsened，with only slight initial weight loss and minimal subsequent change. Both models shared common gross and histopathological features，including partial hepatic cirrhosis，hepatocellular necrosis，portal fibrosis，inflammatory cell infiltration，and bile duct proliferation. However，these features appeared earlier and were more pronounced in the BDL group，whereas the ANIT group showed milder early changes that progressively intensified as the study progressed. Serum biochemical analysis revealed significant elevations in hepatic transaminase levels in both groups（P ＜ 0.05）. In the BDL group，early ALP and TBIL levels were significantly higher than those in the control group （P ＜ 0.05）and markedly exceeded those in the ANIT group（P ＜ 0.05）. In the ANIT group，ALP and TBIL levels were only mildly elevated in the early stage but gradually increased in later stage（P ＜ 0.05）. Analysis of serum inflammatory cytokines showed that IL-1β， IL-6，and MCP-1 levels were significantly higher in the BDL group than in the control group in the early stage（P ＜ 0.05），while in the ANIT group，cytokine levels increased only slightly at first and then gradually rose to levels comparable to those of the BDL group by the later stages（P ＞ 0.05）. After two weeks of SCFA treatment，no significant improvement was observed in jaundice，weight loss， serum liver function markers（ALT，AST，ALP，and TBIL），or inflammatory cytokine levels（IL-6 and MCP-1）in the BDL group（P ＞ 0.05）. Conversely，SCFA treatment in the ANIT group significantly alleviated jaundice and weight loss（P ＜ 0.05）and reduced ALT，AST， and TBIL levels（P ＜ 0.05）. Furthermore，SCFA intervention markedly decreased IL-1β，IL-6，and MCP-1 levels in the ANIT group （P ＜ 0.05）. Conclusion：The BDL model，characterized by rapid onset and severe liver injury，is suitable for studying acute cholestatic liver injury，whereas the ANIT model，with its gradual onset and progressively worsening liver damage，is more appropriate for simulating chronic cholestatic liver injury.