Angiotensin II type 1 (AT1) receptor signaling has been implicated in cerebral microvascular alterations associated with ischemia, diabetes mellitus, hypercholesterolemia, and atherosclerosis. Platelets, which express AT1 receptors, also appear to contribute to the thrombogenic and inflammatory responses that are elicited by these pathologic conditions. This study assesses the role of AT1 receptor activation on platelet-leukocyte-endothelial cell interactions elicited in cerebral microvasculture by ischemia and reperfusion. Intravital microscopy was used to monitor the adhesion of platelets and leukocytes that were labeled with different fluorochromes, while dihidorohydoxyrhodamine 123 was used to quantify oxygen radical production in cerebral surface of mice that were either treated with the AT1 receptor agonist Val-angiotensin II (Ang II) or subjected to bilateral common carotid artery occlusion (BCCAO) followed by reperfusion. Ang II elicited a dose- and time- dependent increase in platelet-leukocyte-endothelial cell interactions in cerebral venules that included rolling platelets, adherent platelets on the leukocytes and the endothelial cells, rolling leukocytes and adherent leukocytes. All of these interactions were attenuated by treatment with either P-selectin or PSGL-1 antibody. The AT1 receptor antagonist candesartan and losartan as well as diphenyleneiodonium, an inhibitor of flavoproteins including NAD(P)H oxidase, significantly reduced the platelet-leukocyte-endothelial cell interactions elicited by either Ang II administration or BCCAO/reperfusion. The increased oxygen radical generation elicited by BCCAO/reperfusion was also attenuated by candesartan. These findings are consistent an AT1 receptor signaling mechanism that involves oxygen radical production and ultimately results in P-selectin- and PSGL-1-mediated platelet-leukocyte-endothelial cell interactions in the cerebral microcirculation.