Abstract: Objective: To investigate the effects of genistein on homocysteine-mediated endothelial cell toxicity and inflammatory response and the underlying mechanisms of such effects.Methods: MTT assay was used to detect cell viability,changes in the morphology of cells were observed under microscope;ELISA assay was used to examine the levels of IL-6 and ICAM-1.Results: The viability of cells treated with 5.0 mmol/L of Hcy was lower than that of other groups,and the difference was statistics significance compared with the control group(P<0.01).ECV-304 cells were identified by their typical cobblestone morphology when viewed by light microscope in control group,the state of cells was also better,but the arrange of cells became disorderly,congregate with 5.0 mmol/L of Hcy in test groups,and the state was the worst.ELISA showed that homocysteine(5.0 mmol/L) significantly increased the expression of IL-6 and ICAM-1,compared with the control group(P<0.01).However,pretreatment with genistein(10,50,100 μmol/L) reversed the decreased cell viability,improved the state of cells in a large extent,and suppressed an increase of expressions of IL-6 and ICAM-1 of cells induced by homcysteine markedly,especially the 100 μmol/L of genistein(P<0.01). Conclusions: Genistein inhibits homocysteine-induced endothelial dysfunction and inflammatory response obviously.