Type 2 diabetes (T2D) is a major risk factor for cardiovascular disease (CVD) development and associated mortality. In the cerebral circulation, T2D-related vascular disfunction also contributes to diverse cerebrovascular diseases including stroke, cognitive impairment, and dementia. Previous research has documented that endothelial dysfunction and inward remodeling are prevalent pathophysiological characteristics of the arterial circulation in T2D. We have further documented that reduced presence of endothelial insulin receptor alpha (IRα) contributes to impaired insulin-dependent vasodilation in omental arteries from T2D patients. Herein, we tested the hypothesis that, compared to wild-type (WT) mice, diabetic db/db mice have reduced insulin-induced vasodilation of the posterior cerebral artery (PCA) in association with reduced presence of endothelial IRα and inward remodeling. We used pressure myography in isolated PCAs to assess vascular reactivity and remodeling, and confocal microscopy to determine IRα content on the endothelial surface. All reported differences are significant at P<0.05. Our results indicate that, when compared with WT controls, PCAs from db/db mice have reduced insulin-induced vasodilatory responses in association with reduced presence of endothelial IRα, inward remodeling, and increased arterial stiffness. The amount of IRβ, elastin, or collagen present in the PCAs did not differ between groups. These findings provide evidence of cerebrovascular endothelial dysfunction in the form of impaired insulin-induced vasodilation in db/db mice, a defect likely attributed to the reduced presence of endothelial IRα and associated with vascular inward remodeling. These changes may contribute to cerebrovascular disease development and progression in T2D, including stroke, cognitive impairment, and associated dementias. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.