Abstract: Objective To explore the protective role of resveratrol by gene expression profiles in tumor necrosis factor-α（TNF-α）stimulated human umbilical vein endothelial cells（HUVEC）. By comparing and analyzing the key regulatory genes to explore the possible molecular mechanism of resveratrol on cardiovascular diseases. Methods Enzyme linked immunosorbent assay（ELISA）was used to measure interleukin-6（IL-6）and monocyte chemoattractant protein-1（MCP-1）levels in cultural supernatant.Co-culture method of monocytes and endothelial cells was used to evaluate cell migration. For gene expression analysis, RNA samples with different stimulants were collected. All samples were hybridized on a 12×135 K NimbleGen gene expression profiles for analysis based on the gene ontology and KEGG pathway analysis databases. Results Without any drug treatment,the concentration of IL-6 and MCP-1 were（346.8±86.0）and（98.82±26.83）ng/L produced by HUVEC.Stimulating HUVEC with10μg/L TNF-α,the concentration of IL-6 and MCP-1 were（183.8±146.7）and（62.57±19.51）ng/L;Adding dose of 10μmol/L resveratrol for intervention,the concentration of IL-6 and MCP-1 were（183.8±146.7）ng/L and（62.57±19.51）ng/L;adding dose of 20μmol/L resveratrol for intervention,the concentration of IL-6 and MCP-1 were（117.0±83.1）ng/L and（55.73±23.34）ng/L. Resveratrol reduced the levels of both IL-6 and MCP-1 in TNF-αinduced HUVEC in a dose-dependent manner. Resveratrol suppressed cell migration and invasion in transwell assay（reduced 30% by 10μmol/L resveratrol,and 80% by 20μmol/L resveratrol,all P＜0.01）. Compared with the TNF-αtreated samples,1604 genes were up-regulated and 2157 genes were down-regulated by pretreated resveratrol. The GO functional analysis indicated that the differentially expressed genes were mainly enriched in reponse to chemical,extracellular stucture organization,extracellular matrix organization,circulatory system development and inflammation response etc. KEGG pathway analysis showed that resveratrol had affected in phosphatidylinositol 3’-kinase/Akt（PI3 K/Akt）pathway and platelet activation signaling pathway,etc. Conclusion Resveratrol can protect HUVEC against inflammation and regulate complex gene expression,alter multiple pathways which may be the potent protective mechanism of resveratrol for preventing vascular diseases.