Objective：This study aims to explore the transformation of Kupffer cells（KCs）in the process of liver ischemia and reperusion and its role in liver ischemia-reperfusion injury. Methods：Mice models of liver ischemia at different time were established. Flow cytometry was used to analyze the number of KCs after ischemia. qPCR was used to analyze the expression of inflammatory cytokines and surface markers of macrophages. Western blotting was used to analyze PI3K/p-Akt2 signaling pathway. After using Akt2 inhibitor before ischemia，the cells were extracted for cell culture in vitro. The expression of inflammatory cytokines and surface markers of macrophages were analyzed by qPCR. In addition，liver injury was analyzed by HE staining of liver slices and serum alanine aminotransferase（ALT） after 6 hours of liver ischemia reperfusion in mice. Results：The number of KCs decreased after ischemia in liver，and the expression of pro-inflammatory cytokines in surviving cells stimulated by LPS was significantly higher than that in control group（P < 0.05），and the expression level of iNOS，a surface marker of M1 macrophages，was also higher than that in control group（P < 0.05）. The PI3K/p-Akt2 signaling pathway in the cells was activated，thus promoting the transformation of KCs to M1 macrophages after ischemia. The transformation can be blocked by Akt2 inhibitor，and it protects liver from ischemia-reperfusion injury. Conclusion：Liver ischemia in mice promotes the transformation of KCs to M1 macrophages through activating PI3K/p-Akt2 signaling pathway and aggravates liver ischemia-reperfusion injury.