The present study was performed to evaluate the cardiovascular effects of ethanolic extract from the root bark of Ulmus macrocarpa (RBUM) in rats. The effects of RBUM on the vascular response of isolated rat aorta and the blood pressure of spontaneously hypertensive rats (SHRs) were evaluated. In addition, its antioxidant activity in H9c2 cells was investigated. In the free radical scavenging assay using 1,1-diphenyl-2-picrylhydrazyl stable free radical (DPPH), RBUM exhibited significant scavenging activity with an EC50 value of 14.3 microg/ml. RBUM also induced resistance to hydrogen peroxide-mediated oxidative insult in H9c2 myocardial cells. In isolated rat aortic preparations, RBUM exhibited potent vascular relaxant effect with an EC50 value of 1.9 microg/ml. This relaxation was significantly inhibited by denudation of the endothelial layer, pretreatment with NG-nitro-L-arginine methyl ester (10 microM), raising extracellular K+ (45 mM), and pretreatment with tetraethylammonium (10 mM). In an antihypertensive study with SHRs, long-term administration with RBUM (100 mg/kg) for 42 d decreased systolic blood pressure (approximately 20 mmHg). In SHRs after 42 d of treatment, RBUM recovered aortic relaxation to acetylcholine and sodium nitroprusside, and attenuated lipid peroxidation in liver of SHRs. These results suggest that chronic treatment with RBUM exerts antihypertensive effects in SHRs, and its direct vasorelaxant and antioxidant properties may contribute to reduce elevated blood pressure.