Based on these studies, modulating KLF2 expression or function could be a novel strategy for the prevention and treatment of inflammatory related disease including atherosclerosis2, 6, 9. Thus, the aim of this study is to screen small-molecule activators that modulate KLF2 expression. Based on luciferase-based assay, we identified that a small molecule drug tannic acid (TA) was a novel KLF2 activator. TA is a specific commercial form of tannin (a type of plant polyphenol). Previous studies showed that TA reduced aortic lesion formation in Apo E −/− mice19. However, the anti-inflammatory action of TA in ECs has not yet been investigated. In the present study, we provide evidence that TA induces endothelial KLF2 expression and thereby attenuates vascular endothelial inflammation. Collectively, our findings not only identified TA as a novel KLF2 activator but also demonstrated that KLF2 could serve as a promising therapeutic target for the treatment of atherosclerosis.