Objective-To evaluate endothelial repair processes in denuded pial vessels to clarify mechanisms for reconstructing endothelium (because endothelial repair of the cerebral artery after its damage is critical for the prevention of thrombosis, the maintenance of vascular tone, and the protection of the brain by the blood-brain barrier). Methods and Results-Endothelial cells (ECs) in a 350-m-long segment of the middle cerebral artery were damaged through a photochemical reaction. Tie2-green fluorescent protein transgenic mice were used for the identification of ECs. Six hours after the endothelial damage, ECs were detached from the luminal surface of the damaged artery, which was then covered with a platelet carpet. Within 24 hours, recovery of the denuded artery started at both edges, with EC elongation and migration. The repair rate was faster at the proximal edge than at the distal edge. Reendothelialization with EC proliferation peaked at 2 to 3 days and ended at 5 days, together with normalization of EC length, with no apparent involvement of foreign progenitor cells. Conclusion-Our in vivo study demonstrated a stepwise reendothelialization process by resident ECs of the pial artery.The prevention of thrombosis, vasospasm, and treatment for blood-brain barrier dysfunction should be considered during the reendothelialization period. Key Words: Tie2 Ⅲ reendothelialization Ⅲ pial artery Ⅲ confocal laser microscopy Ⅲ photochemical reaction B ecause endothelial damage and subsequent exposure of subendothelial tissue in the cerebral artery quickly induces a luminal thrombus and disturbs cerebral blood flow, urgent endothelial repair is critical to minimize ischemic damage, especially after rupture of an atherosclerotic plaque, commonly observed at the carotid artery and the intracranial cerebral arteries. Reendothelialization is also essential to recover normal vascular tone controlled by vasodilatory mediators, such as nitric oxide released from the endothelium. Furthermore, loss of the endothelial tight junction results in breakdown of the blood-brain barrier, causing vasogenic edema. Therefore, restoration of endothelial function in the cerebral vessel is an urgent process for the brain.Endothelial damage of the cerebral artery is a key mechanism involved in the pathophysiology of various brain diseases, including stroke, atherosclerosis, 1 diabetes mellitus, 2 dyslipidemia, 3 hypertension, 4 vasculitis, 5 multiple sclerosis, 6 radiation necrosis, 7 and drug adverse effects. 8 Some markers of endothelial damage are good indicators for the future incidence of cardiovascular events, including stroke. 9 Carotid endarterectomy, a treatment for carotid stenosis, removes atheroma and endothelial cells (ECs), exposing subendothelial tissue. 10 In these conditions, endothelial repair is one of the major targets of treatment.Histological evaluation of reendothelialization and neointima formation after mechanical carotid denudation was previously reported. 11-13 However, the dynamic and minute process of endothelial repair...