Mounting evidence support that KLF2 is an anti-inflammatory and anti-atherosclerotic molecule. Thus, modulating KLF2 expression or activity could be a new therapeutic strategy for inflammatory-related disease such as atherosclerosis. Until now, there are some small molecules which have been reported to regulate KLF2 expression or activity. It has been reported that statins induce the KLF2 expression via MEF221. Statins induce eNOS and thrombomodulin and exert endothelial atheroprotective effects dependent on transcriptional regulator KLF2, and thereby provides a novel mechanism for the beneficial effects of statins in cardiovascular disease21, 24. Moreover, it has been shown that the sirtuin 1 (SIRT1) activator resveratrol increases the expression of KLF2 via MEK5/MEF2 pathway in human endothelial cells, which helps us further understand the role of the SIRT1 activators in regulation of endothelial dysfunction-related cardiovascular disease and aging25. In addition, rapamycin, an mTOR inhibitor, could induce the expression and activity of KLF2, which might counteract coronary endothelial dysfunction27, 28. Taken together, these studies demonstrate that KLF2 may be a novel molecular target for modulating endothelial function. In this study, we performed high throughput screening and identified TA is a new KLF2 activator. We further showed that TA inhibited endothelial inflammation through upregulation of endothelial KLF2 expression and hence downregulation of adhesion molecule VCAM1 expression. Our results provide new insight into the mechanisms whereby TA attenuates vascualr inflammation and atherosclerosis.