Type 2 diabetes (T2D) is a known risk factor for cerebrovascular diseases including Alzheimer’s disease (AD), and vascular dementia (VaD). Yet, our understanding of the mechanisms whereby T2D contributes to neurodegeneration and VaD remains poorly defined. In this present work, we utilized the db/db murine model of T2D and single nuclei RNA sequencing to determine the effect of T2D on endothelial cell-specific transcriptomic changes in the hippocampus, an important brain memory center.