Abstract： Objective To observe the effect of mesenteric lymph duct ligation (MLDL) on systemic inflammatory response syndrome (SIRS) and systemic complications in severe acute pancreatitis (SAP) in rats. Methods Twenty-four Sprague-Dawley (SD) male rats were randomly divided into sham operation group, SAP group, and SAP+MLDL group, with 8 rats in each group. Sham operation group underwent laparotomy only. SAP complicated with multiple organ injury model was reproduced by retrograde injection of sodium taurocholate into the pancreatic duct in SD rats. In SAP+MLDL group MLDL was performed before reproduction of SAP. Rats were sacrificed at 24 hours after operation. The terminal ileums were collected for examination under light microscope. The samples of pancreas, lung and liver were collected for measuring the level of myeloperoxidase (MPO). The mesenteric lymph nodes were harvested for standard bacteriologic culture. The blood levels of diamine oxidase (DAO), D-lactate, endotoxin, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were also measured. Results The blood levels of DAO [(0.64± 0.17) kU/L vs. (0.37±0.07) kU/L], D-lactate [(8.16±1.79) ng/L vs. (3.24±1.00) ng/L], endotoxin [(0.068±0.019) kEU/L vs. (0.033±0.009) kEU/L], TNF-α[(65.21±13.38) ng/L vs. (22.16± 5.04) ng/L] and IL-6[(7.95±1.83) ng/L vs. (4.26±1.23) ng/L] in SAP group were increased significantly comparing with those in sham operation group (all P<0.01). The contents of pulmonary tissue [(9.07±2.52) U/g vs. (4.38+1.29) U/g], pancreatic [(5.14±1.24) U/g vs. (2.88±0.75) U/g] and liver[(6.36±1.63) U/g vs. (3.19±0.96) U/g] MPO were increased significantly in SAP group comparing with those in sham operation group (all P<0.01). The rate of bacterial translocation to mesenteric lymph nodes in SAP group was significantly higher than that of the sham operation group (75.0% vs. 0, P< 0.01). Compared to SAP group, the contents of DAO [(0.50±0.13) kU/L], D-lactate [(6.23± 1.25) ng/L], endotoxin [(0.048±0.014) kEU/L], TNF-α(48.50±13.23) ng/L] and IL-6 [(6.06± 1.64) ng/L] were significantly decreased in SAP+MLDL group (P<0.05 or P<0.01). The levels of pulmonary [(6.58±1.96) U/g], pancreatic [(4.01±1.05) U/g] and liver [(4.64±1.34) U/g] MPO, as well as the rate of bacterial translocation to mesenteric lymph nodes (12.5%) were significantly lower in SAP+MLDL group than those in SAP group (all P<0.05). Conclusion MLDL decreases bacteria/ endotoxin translocation and reduces the systemic inflammatory response by interrupting the lymph flow from the injured gut into the bloodstream. This procedure may protect the small intestine mucosal barrier function and other organs by reducing the neutrophil aggregation and the release of cytokines.