Objective To study the modulation in number and function of endothelial progenitor cell ( EPC ) in multiple organ dysfunction syndrome ( MODS ) after trauma in swine, and to investigate its pathogenesis. Methods Forty pigs were divided into sham group and MODS group ( each, n = 20 ). The model of MODS of two-hit injury, namely hemorrhagic shock and endotoxemia, was reproduced. The peripheral blood was collected before hemorrhage ( T1 ) and endotoxin injection ( T2 ), and 1 hour ( T3 ), 24 hours ( T4 ), 48 hours ( T5 ) after endotoxin injection. Phosphorylation of p38 mitogen-activated protein kinase ( p-p38MAPK ) in mononuclear cell was determined by Western Blot, the content of tumor necrosis factor-α ( TNF-α) was determined with enzyme linked immunosorbent assay ( ELISA ), and the number of EPC was determined with flow cytometry. Results Model of MODS was successfully reproduced in 17 pigs. In model group, the expression of p-p38MAPK ( A value ) peaked at T3 ( 4.83±0.52 ), and gradually declined at T4 and T5 ( 4.36±0.43, 1.93±0.33 ), and the expression of p-p38MAPK at T3-T5 was significantly higher than that at T1 ( 1.00±0.22, all P<0.01 ). The plasma concentration of TNF-α( ng/L ) at T3 in MODS group was obviously elevated compared with that of sham group ( 532.43±52.17 vs. 129.03±20.45, t=31.163, P<0.001 ), and it peaked at T3, it then gradually lowered, and it was significantly higher at T4 and T5 than that in sham group ( T4: 398.93±35.75 vs. 131.12±29.53, t = 26.562, P < 0.001; T5: 287.48±27.26 vs. 126.44±26.96, t=17.861, P<0.001 ). The number of EPC ( ×107/L ) was apparently increased in MODS group at T3 compared with sham group ( 4.832±0.624 vs. 3.545±0.363, t=9.542, P<0.001 ), and it peaked at T3, then gradually decreased, and the number of EPC at T4 and T5 was significantly lower than that in sham group ( T4:2.628±0.627 vs. 3.442±0.325, t=5.043, P<0.001;T5:2.203±0.711 vs. 3.471±0.323, t=2.972, P<0.001 ). Conclusion Phosphorylation of p38MAPK could increase the plasma concentration of TNF-αand decrease the quantity of EPC in MODS,which may be one of the mechanisms of MODS.