Aim To investigate the protective effect of grasp seed procyanidins (GSP) on homocysteine(HCY)-induced cell viability in human umbilical vein endothelial cell(HUVEC) and related molecular mechanisms. Methods Cell viability was analyzed by using MTT and lactate dehydrogenase(LDH) assay.The levels of superoxide dismutase(SOD),glutathione peroxidase(GSHPx) and malondialdehyde(MDA) were examined by kits and the level of intracellular reactive oxygen species(ROS) were determined by flow cytometric assay.Proteins and phosphorylation levels were examined by Western blot. Results Treatment of cultured HUVEC with HCY for 48 hours induced a significant decrease of cell viability.The levels of intracellular ROS and MDA were enhanced,and the activities of SOD and GSHPx were decreased.However,simultaneous treatment with GSP exhibited cytoprotective effects,reduced formation of the MDA and ROS,maintained the activity of SOD and GSHPx,prevented the phosphorylation of exrtacellular signal regulated kinase(ERK),p38 and c-Jun N-terminal kinase(JNK). Conclusion These results demonstrated that GSP had the protective capacity to antagonize HCY induced cell toxicity in HUVEC.The protective effect of GSP may be partially dependent on an anti-oxidative stress effects and then inhibition of the activation of mitogen-activated protein kinase(MAPK).