Scutellaria baicalensis Georgi is an extensively used medicinal herb for the treatment of hypertension in traditional Chinese medicine. Baicalin is the most abundant flavone compound present in Scutellaria baicalensis Georgi and endothelium-dependent vascular activities of baicalin have been suggested. However, the pharmacological implications and mechanisms of baicalin under hypertensive conditions remain to be investigated. The current study examined the blood pressure-lowering effect of baicalin in a spontaneously hypertensive rat (SHR) model. Moreover, vascular activities and mechanisms of baicalin were investigated under hypertensive conditions. The results demonstrate that baicalin treatment lowers the blood pressure in SHRs in vivo. Ex vivo vascular reactivity assay reveals that baicalin relaxes phenylephrine (PE)-constricted SHR aortas in an endothelium-independent manner. Baicalin attenuates Angiotensin II (Ang II) or potassium chloride (KCl)-induced vasoconstriction in SHR aortas as well. Baicalin also relaxes SHR aortas in the presence of different Ca²⁺ channel blockers such as nifedipine and SKF96365 in response to PE-induced constriction. Most importantly, ATP-sensitive potassium channel (K_ATP) blockade partially abrogated the vasorelaxant effect of baicalin. In summary, the current study demonstrates for the first time that intracellular Ca²⁺ regulation in vascular smooth muscle is mechanistically implicated in the vasorelaxant effect of baicalin under hypertensive conditions. Furthermore, activated K_ATP channels are in part required for the vasorelaxant effect of baicalin under hypertensive conditions. Thus, the work here sheds novel pharmacological and mechanistic insights into the blood pressure-lowering effect of baicalin, which may help better understand the therapeutic application of Scutellaria baicalensis Georgi in the treatment of hypertension.