The effects of an aqueous extract of Zygophyllum coccineum L. on rat blood pressure (BP) and on the mesenteric vascular bed were investigated. The extract dose‐dependently reduced BP and heart rate in normotensive and spontaneously hypertensive rats (SHRs). It also reduced BP in pithed SHRs. In vitro , the extract had no effect on basal perfusion pressure of the mesenteric vascular bed. When the perfusion pressure was raised with noradrenaline or potassium chloride, the extract produced a dose‐dependent reduction in perfusion pressure. However, in preparations in which the perfusion pressure was raised with KCl, the depressor response to lower doses of the extract was abolished while higher doses produced responses that were reduced in magnitude when compared with similar responses in preparations in which the perfusion pressure was raised with noradrenaline. It was concluded that extracts of Z. coccineum possess significant antihypertensive activity that may involve some membrane hyperpolarization.