Abstract: Panax ginseng has distinct and impressive health benefits, such as improved blood pressure and immune system functioning. Rg3-enriched Korean red ginseng (REKRG) isolated from Korean red ginseng contains a high percentage of Rg3. In this study, we examined the effects of REKRG on eNOS activation and adhesion molecules in endothelial cells and vascular function in rats. REKRG dose-dependently increased endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production in endothelial cells. In addition, REKRG markedly inhibited the TNF-α-mediated induction of intercellular adhesion molecule (ICAM)-1 and cyclooxygenase (COX)-2 expressions in endothelial cells. REKRG improved endothelium-dependent vasorelaxation in Wistar-Kyoto rat (WKY) and spontaneously hypertensive rats (SHRs) compared with controls. Furthermore, REKRG treatment for 6 weeks increased serum NO levels and reduced the mean aortic intima-media thickness compared with controls. Taken together, these results suggest that REKRG increased vascular function and improved immune system functioning. Therefore, REKRG is a very useful food for preventing or improving various cardiovascular diseases.