Purpose The purpose of this study was to investigate the effect of dexmedetomidine (DEX) on hypotension-induced neuronal damage in a chronic cerebral hypoperfusion (CCH) model of rats, an established model of cerebral white matter lesions (WML) in humans, which is prevalent in the elderly and closely related to cognitive decline. Methods The CCH model rats were randomly assigned to one of four groups: normotension + no DEX (NN) group (n = 6), normotension + DEX (ND) group (n = 6), hypotension + no DEX (HN) group (n = 6), or hypotension + DEX (HD) group (n = 6). Under isoflurane anesthesia, mean arterial blood pressure was maintained at or above 80 mmHg (normotension) or below 60 mmHg (hypotension) for a duration of two hours. The DEX groups received 50 μg of DEX intraperitoneally. Two weeks later, the Y-maze test and, after preparing brain slices, immunohistochemical staining were performed using antibodies against neuronal nuclei (NeuN), microtubule-associated protein 2 (MAP2), glial fibrillary acidic protein (GFAP), and Ionized calcium-binding adapter molecule 1 (Iba1). Results Behavioral observations showed no significant differences among the groups. Significant reductions of both NeuN-positive cells and the MAP2-positive area were found in the hippocampal CA1 in the HN group compared with NN and ND groups, but not in the HD group. GFAP and Iba-1-positive areas were significantly increased in the HN group, but not in the HD group. Conclusion DEX significantly ameliorated hypotension-induced neuronal damage and both astroglial and microglial activation in the CA1 region of CCH rats.