White matter lesions (WMLs) are common in older adults and can lead to cognitive decline and dementia. The neuroinflammation caused by chronic cerebral hypoperfusion (CCH) significantly contributes to WMLs. Peripherally derived mononuclear macrophages are implicated in the development of neuroinflammation. In order to further explore the blood molecules that promote the migration of peripheral monocytes to the site of white matter damage, we applied DIA quantitative proteomic approach to analyze differential serum proteins in WMLs patients and model rats.