Aim To investigate the effects of Stichopus Variegates on tumor necrosis factor-alpha(TNF-α) that induced expression of vascular cell adhesion molecule-1(VCAM-1) and intercellular adhesion molecule-1(ICAM-1) in rat vascular smooth muscle cells(VSMC),and to explore the mechanism of anti-atherosclerosis role of Stichopus Variegates. Methods VSMC were isolated from the media of normal rat thoracic aorta,VCAM-1 and ICAM-1 protein and mRNA expression were detected by flow cytometric technique and reverse transcription-polymerase chain reaction (RT-PCR) respectively.Adhesion of monocytes to VSMC was measured by cell adherence assay. Results Under basal conditions of cultivation,both mRNA and protein expression of VCAM-1 and ICAM-1 in VSMC were very low.Treatment of VSMC with TNF-α(10 μg/L) led to a markedly increase in both VCAM-1 and ICAM-1 expression(p<0.01).Stichopus Variegates(1.5～6.0 g/L) significantly inhibited TNF-α-induced protein and mRNA expression of VCAM-1 and ICAM-1.Flow cytometry showed mean fluorescence intensity of VCAM-1 decreased from 176.4±3.5 to 80.7±1.9(p<0.01),ICAM-1 decreased from 92.2±2.9 to 58.3±2.1(p<0.01);Relative optical density of VCAM-1 decreased from 0.61±0.03 to 0.41±0.04 analyzed by RT-PCR(p<0.01),ICAM-1 decreased from 0.41±0.01 to 0.30±0.03(p<0.05).Cell adherence assay showed that Stichopus Variegates effectively reduced monocytes adhesion to VSMC,OD value decreased from 0.467±0.062 to 0.256±0.029(p<0.05). Conclusion Stichopus Variegates inhibited TNF-α-induced expression of VCAM-1,ICAM-1 and adherence of monocyte to VSMC,which may play important roles in the prevention of atherosclerosis and inflammatory response in vivo.