AIM: To study the effect of blocking intestinal lymphatic circulation in two-hit rats and explore the significance of intestinal lymphatic circulation in two-hit.METHODS: Wistar rats were divided equally into three groups: mesenteric lymph duct ligation group, nonligation group and sham group. Mesenteric lymph was diverted by ligation of mesenteric lymph duct, and the two-hit model was established by hemorrhage and lipopolysaccharide (LPS) methods. All rats were sampled for serum pre-experiment and 24 h postexperiment. The organs including kidney, liver, lung and heart were collected for pathomorphologic observation and biochemical investigation. The nitric oxide (NO),malondialdehyde (MDA) and superoxide dismutase (SOD)were determined in serum and tissue homogenate.RESULTS: Pathomorphology study showed that the structures of kidney, lung, liver and heart tissues were normal in sham group; congestion, degeneration and necrosis in non-ligation group; but only mild lesions in ligation group. After two-hits, the contents of AST, ALT,BUN, Cr and LDH-1 in the serum of non-ligation group and ligation group were obviously higher than that in pre-experiment group and sham group, but obviously lower than that in non-ligation group. The contents of NO2-/NO3-, NOS, iNOS and MDA in the serum of nonligation group were significantly increased, compared with pre-experiment and sham group, but SOD was significantly lower. These parameters were significantly different in ligation group compared with that in sham group, but NO2-/NO3-, iNOS and MDA in ligation group were significantly lower than that in non-ligation group.CONCLUSION: Ligation of mesenteric lymph duct could improve the disturbance of organic function and morphologic damage in two-hit rats; the lymphatic mechanism in two-hit should be emphasized.