〔Abstract〕 Objective To reveal the effect of lipopolysaccharide-binding protein(lbp) gene on sepsis in rats and its important regulatory mechanism. Methods The acute liver inflammatory injury model was induced by lipopolysaccharide(LPS). The levels of serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected by biochemical analyzer to evaluate the liver injury, and the proinflammatory factors TNF-α and IL-6 were detected by RT-PCR to evaluate the level of inflammation, liver hematoxylin-eosin staining was used to observe the infiltration of inflammatory cells and hepatocyte injury in liver tissue. RNA-Seq was performed to compare the transcriptome expression differences betweenlbpgene knockout(lbp-/-) rats and wild-type(WT) rats to excavate the downstream genes regulated bylbpin LPS induced liver inflammatory injury. The biological process and signal pathway were explored by GO function annotation and KEGG enrichment analysis. RT-PCR was used to verify the mRNA expression level of differential genes. Results Compared with WT group, the levels of ALT, AST and pro-inflammatory factors in serum oflbp-/-rats decreased(P<0.05), and histological observation showed that the infiltration of inflammatory cells decreased. Transcriptomic analysis of liver tissue showed that 168 genes were differentially expressed afterlbp-/-(P<0.05), among whichCyp7 a1、Cyp4 a2and other up-regulated genes were enriched in peroxisome proliferator activated receptor(PPAR) signal pathway and steroid hormone synthesis pathway(P<0.05). Conclusion lbp-/-may participate in biological processes such as bacterial clearance and lipid metabolism by promoting PPAR signal pathway, so as to reduce liver inflammatory injury and slow down the occurrence and development of sepsis.