Aim To investigate whether dehydroepiandrosterone(DHEA) can retard atherosclerosis formation by inhibiting the expression of vascular cell adhesion molecule-1(VCAM-1) and whether all-trans retinoic acid can promote this action. Methods The rabbits were fed with high cholesterol diets for 10 weeks.Then serum lipid levels of all rabbits were measured and the aorta was sampled for morphological observation.Using immunohistochemistry and reverse transcription polymerase chain reaction(RT-PCR),the effect of DHEA on the expression of VCAM-1 protein and mRNA were determined in the aorta of high cholesterol-fed rabbits.In vitro cultured THP-1 monocytes,the expression of VCAM-1 protein and mRNA intervened by DHEA in different density were determined by immunocytochemistry and RT-PCR. Results The thickness of the aortic tunica intima and the aorta atherosclerosis plaque area in the rabbits intervened by DHEA were lowered by 59% and 48% compared with high cholesterol-fed rabbits.The expressions of VCAM-1 protein in the rabbits intervened by DHEA(0.1920±0.0034) were reduced significantly compared with high cholesterol-fed rabbits(0.3846±0.0198).And the expression of VCAM-1 mRNA in the rabbits intervened by DHEA(0.6856±0.0286)were also reduced significantly compared with high cholesterol-fed rabbits(1.0893±0.1089).In vitro cultured THP-1 monocytes,when DHEA in different dose was added into the medium simultaneously,oxidized low density lipoprotein(ox-LDL)-induced VCAM-1 expression was decreased.The expressions of VCAM-1 mRNA in the THP-1 monocytes intervened by DHEA(0.2988±0.0312) were reduced significantly compared with ox-LDL-induced THP-1 monocytes(0.6236±0.0237)when DHEA is 5 μmol/L. After all-trans retinoic acid was added,the change of each index wasn't obvious(p<0.05). Conclusions DHEA showed inhibiting effects on the VCAM-1 expression in both the aorta of high cholesterol-fed rabbits and ox-LDL-induced THP-1 monocytes. That may be one of the mechanisms of antiatherosclerotic action of DHEA. But all-trans retinoic acid have no obvious effect on the VCAM-1 expression in this action.