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This study measured stimulus-evoked brain tissue oxygenation changes in a mouse model of Alzheimer disease (AD) and further explored the influence of exercise and angiotensin II-induced hypertension on these changes. in vivo two-photon phosphorescence lifetime microscopy was used to investigate local changes in brain tissue oxygenation following whisker stimulation. During rest periods, PO₂ values close to the arteriolar wall were lower in the AD groups and the PO₂ spatial decay as a function of distance to arteriole was increased by hypertension. During stimulation, tissue PO₂ response had a similar spatial dependence across groups. Tissue PO₂ response in post-stimulation period was larger in AD groups (e.g., AD6 and ADH6) than in the controls (WT6 and WTH6). After a 3-month voluntary exercise period, some of these changes were reversed in AD mice. This provides novel insight into tissue …