Background: Psychological stress is known to contribute to cardiovascular diseases such as atherosclerosis. However the underlying mechanism is still unclear. Thus we studied if stress induces endothelial dysfunction and vascular inflammation in the animal model of metabolic syndrome. Methods and Results: Immobilization stress (2 hr/d) using a restrainer was applied for 14 days to the 10-wk (YI2O) and 21-wk OLETF rats (EI2O) and the 21-wk Long-Evans Tokushima Otsuka (LETO) rats (EI2L). Control groups comprise of 10-wk (YCO) and 21-wk OLETF rats (ECO) and 21-wk LETO rats (ECL) without immobilization stress. Immobilization stress significantly increased systolic blood pressure, whereas it decreased weight gain in the OLETF rats. Ex-vivo study showed that acetylcholine-induced vasorelaxation, measured using a myograph in the superior mesenteric artery, was significantly decreased in YI2O, EI2O, and EI2L groups compared with each control. However, nitroprusside-induced vasorelaxation was not significantly different between each stress group and control. The extent of ICAM-1 expression, assessed by immunohistochemical staining in the aorta, was significantly increased in EI2O group vs. ECO group. In the aortas of EI2O group, compared with those of ECO group, expressions of Rho-associated kinase (ROCK)-1, NADPH oxidase p22phox subunit, phosphorylated-IkB慣, assessed by Western Blot, were increased, whereas expression of catalase was decreased. Conclusions: Immobilization stress induces systolic hypertension, endothelial dysfunction, and vascular inflammation via oxidative stress by activation of NF觀B, increased activity of NADPH oxidase and ROCK-1, and decreased catalase in the OLETF rats.