Objective: To investigate the relationship between intestinal endotoxin (ET) and liver expression of Toll-like receptor 4 (TLR4) in liver injury induced by severe acute pancreatitis (SAP). Methods: Forty-eight Wistar rats were equally randomized into model group and control group. Rats in model group were subjected to retrograde cholangiopancreatic duct injection of 5% sodium taurocholate to induce SAP, while rats in control group underwent sham operation. At 3, 6 and 12 h after surgery, 8 rats at each time point were randomly taken from each group, and their pancreatic and liver tissues as well as peripheral arterial blood samples were collected. Pathological examinations were performed, and the blood levels of amylase (AMY), alanine transaminase (ALT) and ET, as well as the TLR4 expression in liver were determined. Results: Compared with control group, the pathological scores for pancreatic and liver injury, blood levels of AMY, ALT and ET, and liver expression level of TLR4 protein in model group were all increased significantly (all P<0.05), and all above parameters were increased in a time-dependent manner. All the parameters in control group showed no significant alteration across time points (all P>0.05). In model group, there was a significant positive correlationship between liver TLR4 expression and blood ET level (r=0.863, P<0.01). Conclusion: Blood ET level increase is correlated with liver TLR4 up-regulation during SAP, and the interaction between ET and TLR4 may be involved in the mechanism of SAP-induced liver damage.