Objective To investigate the protective effect of aprotinin on liver injury in septic rats and its mechanism. Methods Thirty male SPF rats were randomly divided into sham operation group, cecum ligation and puncture (CLP) group and aprotinin intervention group (10 rats in each group). The sham operation group was treated with cecal exploration, CLP group and aprotinin group were treated with CLP method to establish sepsis rat model. The rats in each group were sacrificed 24 hours after operation, and the morphological changes of liver tissue in rats were observed, the serum liver function indicators and inflammatory cytokines levels were detected, and the protein expression of Toll-like receptor (TLR4)/nuclear factor κB (NF-κB) signaling pathway in liver tissue was detected. ResultsIn the CLP group, septic rats exhibited significant inflammatory cell infiltration in hepatic tissue and disordered hepatocyte morphology. Compared with the CLP group, the aprotinin group exhibited nearly normal hepatocyte morphology with significant improvement in vacuolar degeneration. Compared with the sham operation group, the serum aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor-α, interleukin-6 were increased, and the expression of TLR4 and p-NF-κB protein in liver tissue was up-regulated in the CLP group (P<0.05). Compared with the CLP group, serum aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor-α, interleukin-6 were decreased, and the expression of TLR4 and p-NF-κB protein in liver tissue was decreased in the aprotinin group (P<0.05). ConclusionAprotinin may play a protective role against sepsis related liver injury by inhibiting TLR4 / NF-κB signaling axis, reducing the production of inflammatory factors and alleviating inflammatory reactions.