Background <p>Connectional “diaschisis” theory indicates that the remote functional network disconnection resulting from focal white matter damage contributes to the cognitive dysfunction in vascular cognitive impairment and dementia (VCID). Acupuncture has been reported to attenuate white matter lesions and improve cognitive dysfunction of VCID individuals. However, whether these benefits are associated with the connectional diaschisis remains unclear.</p> Methods <p>Here, 12-time acupuncture treatment was administered to the rat model of VCID. After behavioral tests, functional and diffusion magnetic resonance imaging were performed to analyze the connectivity of brain networks and white matter integrity. Pathological changes in myelin loss, axon injury, and glial activation were also observed. To clarify the interrelation of function and structure, correlation and mediation analyses were conducted.</p> Results <p>Acupuncture ameliorated spatial working memory loss, reconnected the disruption of the default mode network, and prevented myelin and axon in the corpus callosum from the inflammatory attack. The association between restored corpus callosum integrity and spatial working memory was partially mediated by the increased functional connectivity of the anterior cingulate cortex.</p> Conclusions <p>These evidence suggest that rewiring the corpus callosum-anterior cingulate cortex axis may be an integrated mechanism for the acupuncture effects on brain structure and function in VCID.</p>