Objiective Increased intracellular reactive oxygen species (ROS) is crucial for vascular endothelial dysfunction,a key step in the initiating of atherosclerosis (AS).The antioxidant activity of flavonoids has been suggested to contribute to AS prevention.However,The association of the structure characteristics to antioxidant capacities in relation to the inhibitory effects on endothelial dysfunction has not been well established.Methods and results In this study,four subclasses of flavonoids with similar structures,including two anthocyanins (delphinidin and cyanidin),two flavonols (myricetin and quercetin),two flavones (luteolin and apigenin) and two isoflavones (genistein and daidzein) were examined for their inhibitory effects on intracellular ROS-mediated signaling pathway in the human umbilical vein endothelial cell EA.hy926.Cells were pretreated vith different flavonoids for 2h and then exposed to oxLDL of 100 μg/ml for another 24h.It was found that treatment with different flavonoids alone had no notable effects on cell viability.However,the oxLDL-induced decrease of cell viability,generation of O2-and ROS,p38MAPK activation,NF-κB nuclear translocation,NF-κB-modulated transcriptional activity as well as well as the mRNA expression of genes including ICAM-1,E-selectin,MMP-1,MMP-2 and MMP-9 were notably inhibited by the pretreatment of different flavonoids through blunting ROS-triggered signaling pathway,in spite of apparent differences.And the number of hydroxy1 groups in total,3,4-ortho-dihydroxy1 in B-ring and 3-hydroxy1 group in C-ring of flavonoids were important strucure characteristics for the inhibitory effects.Thus,anthocyanins and flavonols such as delphinidin and myricetin exert higher ROS scavenging activities and more significant endothelium-protective effects compared to the other compounds.Conclusion Our results provide evidence for AS prevention and a basis for designing the potent anti-atherosclerotic agents.