Objective To investigate the mechanism of action of stasis-resolving and collateral-dredging moxibustion in promoting myelin regeneration in rats with vascular dementia (VD) by observing its effect on the phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway.Methods After screening by the Morris water maze test, 12 rats were randomly selected as sham-operation group,and the remaining rats were randomly divided into model group,moxibustion group,and moxibustion+LY294002 group after successful modeling of VD,with 12 rats in each group.The rats in the moxibustion group were given stasis-resolving and collateral-dredging moxibustion,and those in the moxibustion+LY294002 group were given intraperitoneal injection of the PI3K inhibitor LY294002 in addition to stasis-resolving and collateral-dredging moxibustion.The Longa scoring system was used to evaluate the degree of neurovascular injury in rats;the Morris water maze test was used to evaluate the learning and memory abilities of rats;Western blot was used to measure the expression of proteins associated with the PI3K/AKT/mTOR signaling pathway;LFB myelin staining was used to observe the morphology of myelin in the corpus callosum of rats; transmission electron microscopy was used to observe the myelin ultrastructure of rats.Results Compared with the sham-operation group,the model group and the moxibustion+LY294002 group had significant increases in Longa score (P<0.05) and escape latency (P<0.05) and significant reductions in the expression levels of the proteins associated with the PI3K/AKT/mTOR signaling pathway (P<0.05);the myelin in the corpus callosum showed unclear texture,disordered arrangement,vacuolar changes at the edge,and fragmentation with partial protrusions and disintegration,as well as a significant reduction in the number of myelinated nerve axons (P<0.05). Compared with the model group and the moxibustion+LY294002 group,the moxibustion group had significant reductions in Longa score (P<0.05) and escape latency (P<0.05) and significant increases in the expression levels of the proteins associated with the PI3K/AKT/mTOR signaling pathway (P<0.05),with certain recovery of the structure of myelin in the corpus callosum,ordered arrangement,dense structure at the edge,and a significant increase in the number of myelinated nerve axons (P<0.05). Conclusion Stasis-resolving and collateral-dredging moxibustion can repair myelin damage,promote myelin remodeling,and restore white matter function by activating the PI3K/AKT/mTOR signaling pathway.