Objective: To investigate the effect of thoracic duct lymph drainage on lung injury induced by severe acute pancreatitis (SAP) and its mechanism. Methods: Seventy-two SD rats were randomized into sham operation group, SAP model group (SAP group) and SAP model plus thoracic duct lymph drainage group (drainage group). SAP model was induced by retrograde injection of 5% sodium taurocholate into biliopancreatic duct, and rats in drainage group underwent continuous thoracic duct lymph drainage. Eight rats in each group were sacrificed at 4, 8 and 14 h after surgery, respectively. The endotoxin (ET) levels in the lymphatic fluid and plasma were measured, the pathological changes of rats’ lung tissues were assessed and NF-κBp65 protein expressions in lung tissues were also detected. Results: Except for sham operation group, rats in both SAP group and drainage group exhibited remarkable lung injury 8 h later, which in drainage group was less evident than that in SAP group. The lymphatic ET levels in each group showed no significant difference at the 4-h time point, but were increased in both SAP group and drainage group with time prolongation, which were significantly higher than those in sham operation group at 8- and 14-h time points (all P<0.05). The lymphatic ET levels in sham operation group showed no difference at the three observation time points (P>0.05). The change patterns of plasma ET levels in each group were similar to those in the lymphatic fluid, and the plasma ET levels were significantly positively correlated with the lymphatic ET levels (4 h: r=0.7857, P=0.0208; 8 h: r=0.7233, P=0.0426; 14 h: r=0.9048, P=0.0002). The NF-κBp65 protein expression levels showed no significant difference among groups at the 4-h time point, but were significantly increased in both SAP group and drainage group compared with sham operation group at 8- and 14-h time points (all P<0.05). The elevation degrees of NF-κBp65 expression in drainage group were significantly lower than those in SAP group at both time points (both P<0.05). Conclusion: The lymphatic ET and NF-κB expression levels in lung tissues increase significantly in rats with lung injury secondary to SAP, and thoracic duct lymph drainage is a positive treatment modality for this condition.