In this study, the effect of heparin-derived oligosaccharide(HDO)on lipopolysaccharides(LPS)-induced inflammation in human umbilical vein endothelial cells(HUVECs)and the molecular mechanisms were investigated. The generation of intracellular reactive oxygen species(ROS)was detected by 20, 70-dichlorofluorescein diacetate(DCFH-DA). Experiment is divided into blank group(0. 5% serum medium), model group(LPS+0. 5% serum medium)and HDO dosing group(LPS+0. 5% serum medium +0. 01, 0. 1, 1mol/L HDO). The intracellular reactive oxygen species level was detected by reactive oxygen species experiment, the level of key regulatory proteins p38 and p-p38 in MAPK pathways and VCAM-1 were determined by Western blot. The results showed that HDO at 0. 01, 0. 1 and 1 μmol/L could inhibit the expression of VCAM-1 in HUVECs induced by 100 μg/mL LPS, and reduce the expression of key regulatory proteins p38 and p-p38, but could not obviously affect NF-κB nuclear translocation. The results all above showed that HDO could decrease the key regulatory proteins expression, and suppress the transcription of VCAM-1, resulting in inhibiting inflammation.