〔Abstract〕 Objective To investigate the effects of D-allose on the restoration of neurological function, Galectin-3(Gal-3), adenosine monophosphate-activated protein kinase/mammalian target of rapamycin(AMPK/mTOR) and the expression of some inflammatory factors in ischemia-reperfusion injury(CIRI) mice. Methods A total of 50 male mice were randomly divided into control group(Con group), sham group(Sham group), cerebral ischemia-reperfusion injury group(MCAO group), cerebral ischemia-reperfusion injury+D-alolose group(MCAO+D-allose group) and cerebral ischemia-reperfusion injury+modified citrus pectin group(MCAO+MCP group). The middle cerebral artery occlusion/reperfusion(MCAO/R) model(reperfusion after 2 hours of MCA ischemia) was established by thread embolism. After successful modeling, the neurological function of mice was evaluated Longa score and rotated rod walking. TTC staining was used to observe the volume of cerebral infarction foci. The expression levels of Gal-3 and autophagy-related molecules were detected by Western blot and RT-PCR. Immunofluorescence was applied to detect the distribution of Gal-3 in brain tissue, and TNF-α, IL-8 secretion was detected with ELISA KIT. Results Compared with Con group and Sham group, the MCAO model represented significant increase in the Longa neurofunction score(P<0.01), cerebral infarction volume(P<0.01), Gal-3 expression and manifasted enhanced autophagy(P<0.01). After treatment with D-allose, it could significantly improve neurological dysfunction, reduce cerebral infarction volume(P<0.01), reduce the expression of Gal-3(P<0.01), inhibit AMPK phosphorylation, promote mTOR phosphorylation, and inhibit autophagy(P<0.01). The use of the Gal-3 inhibitor MCP alone could also achieve the effect of inhibiting autophagy. Conclusion D-allose can effectively promote the recovery of neurological function and reduce the volume of infarct foci in CIRI mice. The mechanism may involve inhibiting excessive cell autophagy by downregulating the expression of Gal-3, and reducing the release of inflammatory factors such as TNF-α and IL-8, thereby exerting neuroprotective effects.