The vasorelaxant effects of the aqueous extract prepared from the bark of the Chinese medicinal herb, Eucommia ulmoides Oliv. (also referred to as Tu-Chung or Du-Zhong), which is a common active ingredient in traditional antihypertensive herbal prescriptions in China, have recently been characterized in rat aorta and dog carotid artery. The vasorelaxant effect of eucommia bark extract on these large elastic arteries was found to be entirely endothelium-dependent and nitric oxide (NO)-mediated. Since smaller muscular arteries play a more dominant role in the change of peripheral resistance and thus the regulation of blood pressure, we have now compared the relaxant effects of eucommia bark extract using aorta and the proximal as well as the distal ends of the superior mesenteric arteries from the rat, with a specific objective to investigate whether smaller muscular arteries also elicit endothelium-dependent vascular relaxation (EDVR) in response to eucommia bark extract. We have also determined whether the EDVR, if indeed occurring in the mesenteric arteries, is mediated entirely by NO, or whether it also involves endothelium-derived hyperpolarizing factor (EDHF). We found that all three types of vessel preparations elicit EDVR in response to the eucommia bark extract concentration-dependently in a similar manner to the relaxant responses to carbachol (CCh). Although the NO synthase inhibitor L-NAME totally abolished the EDVR in aorta, it only partial abolished EDVR in mesenteric arteries isolated from each end, the distal end being more resistant to L-NAME. However, the residual L-NAME-resistant relaxation of the rat mesenteric arteries could be further inhibited by preincubation of the vessels with the combination of L-NAME and 15-20 mM KCl (KCl itself at this low concentration caused little or no contraction). Therefore, the EDVR induced by the eucommia extract and CCh in aorta is mediated entirely by NO, and that in mesenteric arteries by NO as well as EDHF, with the EDHF component (inhibited by KCl) larger in the smaller distal end of the rat mesenteric artery. Results of our study offer a plausible mechanistic basis for the vasorelaxing action of Eucommia ulmoides Oliv., which may account for its well-documented antihypertensive action.