7-Difluoromethyl-5,4'-dimethoxygenistein (dFMGEN), prepared by the difluoromethylation and alkylation of genistein, is an active new chemical entity. The effects of dFMGEN on cell adhesion and inflammation were investigated in human umbilical vein endothelial cells, and whether its role involved regulation of NF-kappaB expression was also studied. Results demonstrated that pretreatment with dFMGEN decreased the adhesion between vascular endothelial cells and monocytes, reduced the release of E-Selectin, ICAM-1, IL-6 and TNF-alpha in vascular endothelial cells, and down-regulated the expression of NF-kappaB. Therefore, data suggested that dFMGEN can effectually inhibit the adhesion between vascular endothelial cells and monocytes induced by oxidative stress and inflammatory reaction, and its role is connected with the downregulation of NF-kappaB.