We investigated the effects of changing the extracellular potassium as well as magnesium concentration ([K + ] o and [Mg 2+ ] o ) in cerebral penetrating arterioles. The internal diameter of isolated pressurized cerebral penetrating arterioles in rat was measured under the microscope in the low [K + ] o , low [Mg 2+ ] o and high [Mg 2+ ] o , respectively. Vascular responses induced by the low [K + ] o were observed in the absence and presence of several inhibitors. The low [K + ] o produced a biphasic response consisting of an initial transient constriction followed by dilation. The transient constriction was attenuated by Na + –K + –adenosine triphosphatase (ATPase) inhibitor in a concentration-dependent manner and L-type Ca 2+ channel inhibitor but not by all K + channel inhibitors. The low [Mg 2+ ] o significantly induced constriction, whereas the high [Mg 2+ ] o induced dilation. We analyzed that transient constriction in the low [K + ] o may be led by membrane depolarization induced by inactivity in Na + –K + –ATPase. The vasomotor responses of the changing of [K + ] o as well as [Mg 2+ ] o in a cerebral microcirculation may influence the pathological and therapeutic condition in cerebrovascular diseases, and may provide new therapeutic targets.