PurposeMild cognitive impairment (MCI) is a general neurodegenerative disease. Moxibustion has been shown to have remarkable effect on cognitive improvement, however, less is known about the effect of moxibustion on MCI and its underlying neural mechanism. This study aimed to investigate the ameliorative brain network in MCI after treatments of acupoint-related moxibustion. MethodsResting-state functional MRI were derived from 47 MCI patients and 30 healthy controls (HCs). Patients were randomized as Tiaoshen YiZhi (TSYZ, n = 27) and sham (SHAM, n = 20) acupoint moxibustion groups. Functional connectivity density (FCD) method and repeated-measures two-way analysis of variance (ANOVA) were performed to ascertain the interaction effects between groups (TSYZ and SHAM) and time (baseline and post-treatment). Abnormal FCD was examined between baseline and post-treatment in TSYZ and SHAM groups, respectively. ResultsCompared with HCs, MCI showed altered FCD in the middle frontal cortex (MFC), inferior frontal cortex, temporal pole, thalamus and middle cingulate cortex. After moxibustion treatment in MCI, 1) a significant time-by-groups interaction was observed in the medial prefrontal cortex (mPFC); 2) abnormal long-range FCD (lrFCD) in the mPFC and MFC were modulated in TSYZ group; 3) significantly improved clinical symptoms; 4) changed lrFCD in the MFC was significantly negatively correlated with the increased Montreal Cognitive Assessment scores in TSYZ group. ConclusionsThese imaging findings suggest that treatments of acupoint-related moxibustion could improve lrFCD in certain regions related to self-related cognitive and decision making. Our study might promote understanding of MCI neural mechanisms and expand the clinical application of moxibustion in MCI.