Objectives: Receptor for advanced glycation end-product (RAGE) plays a key role in the development of vascular inflammation and acceleration of atherosclerosis in type 2 diabetics. Angiotensin receptor blocker (ARB) or calcium channel blocker (CCB) is commonly used in the treatment of diabetes-related hypertension. Thus we investigated the effect of ARB or CCB on the RAGE expression in the vessel walls of type 2 diabetic rats. Methods: Type 2 diabetic, 25-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were randomized to 8 weeks of gastric gavage of candersartan (CDRT; 3mg/kg; n=8), amlodipine orotate (AMDP; 3mg/kg; n=8) or saline (n=8) after blood pressure (BP) measurement and intraperitoneal glucose tolerance tests (IP-GTT). After 8 weeks, all rats were sacrificed and their aortas underwent immunohistochemical (IHC) analyses for RAGE, dihydroethidium (DHE) staining for oxidative stress and immunoblotting for RAGE and ERK1/2. Results: Both CDRT and AMDP significantly lowered systolic BP than saline treatment (107짹5 vs. 113짹5 vs. 137짹7 mmHg, p<0.05) and postprandial 30-minute glucose levels (317짹42 vs. 305짹54 vs. 418짹19 mg/dL, p<0.05). IHC analyses and immunoblots demonstrated reduced RAGE aortic signals in both CDRT- and AMDP-treated compared to saline-treated OLETF rats (p<0.05, respectively). DHE staining revealed reduced reactive oxygen species (ROS) signals in CDRT- or AMDP-treated rats compared to saline-treated rats (p<0.05). However, CDRT therapy significantly reduced phosphorylated-ERK 1/2 aortic signals compared to AMDP- or saline-treated rats (p<0.05). Conclusion: Both ARB and CCB reduces aortic RAGE expression to the similar magnitude. ARB may reduce aortic RAGE signals by suppressing aortic wall oxidative stress and ERK1/2 pathway. In contrast, inhibition of ROS production may be responsible for AMDP-induced RAGE suppression in the aortic walls of type 2 diabetic rats. Theses results support the potential of ARB or CCB as an anti-atherosclerotic agent in type 2 diabetes.