Background and ObjectiveStroke may cause neuropsychiatric problems, which have negative effects on cognitive functions and behavior. Exercise plays an important role in reducing the occurrence and development of stroke, the concrete mechanism is not fully clarified. In this study, we attempted to determine whether early treadmill exercise attenuates anxiety-like behavior by regulation of inflammation after brain ischemia. MethodWe subjected adult male rats to middle cerebral artery occlusion (MCAO) for 90min and trained rats started to run on a treadmill from postoperative day 1 to day 14. The effects of treadmill on cognitive functions, anxiety-like behavior, and immune activation were analyzed by Morris water maze test, open field test, elevated plus maze test, and enzyme-linked immunosorbent assay. ResultsEarly treadmill exercise significantly improved cognitive function, alleviated anxiety-like behavior in ischemic rats model; this improvement was associated with significantly decreased activation of astrocytes and microglia cells and proinflammatory markers (platelet-activating factor [PAF], interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-], intercellular adhesion molecule-1 [ICAM-1], and vascular cell adhesion molecule-1 [VCAM-1]). ConclusionOur results indicated that early treadmill exercise attenuated anxiety-like behavior by decreasing inflammation response, exercise conferred a great benefit of attenuating anxiety-like behavior via anti-inflammatory treatment may prove to be a novel neuroprotective strategy for stroke.