〔Abstract〕 Objective To explore the changes in cerebral blood flow caused by mandibular retrusion, as well as the impact and potential mechanisms on stroke recovery. Methods 6-week-old SD male rats were selected as experimental subjects. The metal cannula was bonded to the rat maxillary incisor for one week, forcing mandibular retrusion(MR). Cerebral blood flow was detected by laser speckle imaging. Cognitive function was detected by the Morris water. Then, the stroke model was constructed in MR rats by using the middle cerebral artery occlusion(MCAO) method for one week. Meanwhile, metal cannulae were then removed in rats to restore the lower jaw′s position(MCAO RO), serving as a positive control group. Consequently, rats were randomly divided into the following groups: Sham groups, MCAO groups, MCAO MR groups, and MCAO RO groups. Neurological recovery was assessed through the modified neurological severity score(mNSS). The area of cerebral infarction was evaluated by using triphenyltetrazolium(TTC) staining. The changes in nerve cells were observed by using hematoxylin eosin(HE) staining. The protein expression level of vascular endothelial growth factor(VEGF) was detected by immunohistochemistry. The protein expression levels of platelet-endothelial cell adhesion molecule(CD31), sirtuin 6(SIRT6), and thioredoxin interaction protein(TXNIP) were detected by Western blot. The mRNA expression levels of SIRT6, TXNIP, and VEGF were determined by qRT-PCR. Microglia activation marker molecule 1(IBA-1) was detected by immunofluorescence. Resluts Because of mandibular retrusion, laser speckle showed decreased cerebral blood flow, and the water maze showed decreased cognitive function. Compared to other groups, MCAO MR showed a larger ischemic area in TTC staining, while HE staining and neurological scoring showed poorer neurological function recovery. Western blot and qRT-PCR showed that the MCAO MR group inhibited the mRNA and protein expression levels of SIRT6, upregulated the mRNA and protein expression levels of TXNIP, and increased the activation of microglia. Conclusion Mandibular retrusion reduces cerebral blood flow and alters cognitive function in rats. Mandibular retrusion inhibits recovery in stroke through the SIRT6/TXNIP axis.