The sepsis models of cecal ligation and puncture(CLP) in rats and mice were analyzed, and potential sepsis-related genes were found from the perspective of model animals, providing a theoretical basis for diagnosis and treatment of sepsis. After downloading the original microarray data set from the NCBI-Gene Expression Omnibus database (NCBI-GEO), cecal ligation puncture sepsis model and sham operation groups were included. Bioinformatics methods are used to screen differential genes after standardization of data. Then we performed enrichment analysis and pathway analysis, constructed a protein interaction network to screen core proteins and key candidate genes with important physiological regulatory functions. Through the differential gene expression chip screening of liver tissues after cecal puncture in rats, we obtained 350 differential genes that were up-regulated 1.5 times and more, and 1 337 differential genes that were down-regulated 2 times and more. Screening of differential gene expression chips of liver tissues after sepsis induction in mice yielded 3 532 differential genes that were up-regulated 1.5 times or more, and 4 020 differential genes that were down-regulated 1.5 times or more. According to the overlap of the differential genes from the above chip results, 29 differentially expressed genes were up-regulated more than 1.5 times, and 84 differentially expressed genes were down-regulated. Besides performing a protein-protein interaction (PPI) network, biological processes (BP), molecular functions (MF), cellular components (CC) and KEGG(Kyoto encyclopedia of genes and genomes) pathway analysis of gene function on the above genes in the David database, we found that a total of 10 pathways are closely related to sepsis liver tissue. The most important pathway is the MAPK pathway, followed by HIF-1 (hypoxia inducible factor 1), FoxO (forkhead box, sub-group O), hepatitis B, platelet activation and bile regulation of secretory pathways. This provides a theoretical basis for our further research on the pathophysiology and diagnosis and treatment of sepsis.