Aim To investigate the effect of 7-difluoromethyl-genistein(FMGEN) on oxidative stress-induced cell adhesion between vascular endothelial cells and mononuclear cells and the underlying mechanism.Methods Fluorescent light spectrophotometer was used to detect the cell adhesion between vascular endothelial cells and mononuclear cells.The concentrations of E-selectin and intercellular adhesion molecule(ICAM-1) in the cell culture supernatant were determined by enzyme-linked immunosorbent assay(ELISA).The activation of P38 mitogen-activated protein kinase (P38-MAPK) was analyzed by Western blotting.Results Exposure of vascular endothelial cells to H_2O_2 for 24 h increased the adhesion between vascular endothelial cells and mononuclear cells and the release of E-selectin and ICAM-1 in vascular endothelial cells;however,these effects of H_2O_2 were inhibited by FMGEN in a concentration-dependent manner. Treatment of vascular endothelial cells with H_2O_2 for 24 h resulted in the significant activation of P38-MAPK and the activation of P38 induced by H_2O_2 was inhibited by FMGEN.SB203580,a specific inhibitor of P38-MAPK blocked the adhesion between vascular endothelial cells and mononuclear cells and the release of E-selectin and ICAM-1 in vascular endothelial cells induced by H_2O_2.Conclusion FMGEN antagonizes oxidative stress-induced cell adhesion between vascular endothelial cells and mononuclear cells,which is associated with inhibition of the release of E-selectin and ICAM-1 via down-regulating the activation of P38-MAPK.