AIM: To analyze changes in amplitude of low-frequency fluctuations (ALFFs) and default mode network (DMN) connectivity in the brain, using resting-state functional magnetic resonance imaging (rs-fMRI), in high myopia (HM) patients. METHODS: Eleven patients with HM (HM group) and 15 age- and sex-matched non-HM controls (non-HM group) were recruited. ALFFs were calculated and compared between HM group and non-HM group. Independent component analysis (ICA) was conducted to identify DMN, and comparisons between DMNs of two groups were performed. Region-of-interest (ROI)-based analysis was performed to explore functional connectivity (FC) between DMN regions. RESULTS: Significantly increased ALFFs in left inferior temporal gyrus (ITG), bilateral rectus gyrus (REC), bilateral middle temporal gyrus (MTG), left superior temporal gyrus (STG), and left angular gyrus (ANG) were detected in HM group compared with non-HM group (all P<0.01). HM group showed increased FC in the posterior cingulate gyrus (PCC)/precuneus (preCUN) and decreased FC in the left medial prefrontal cortex (mPFG) within DMN compared with non-HM group (all P<0.01). Compared with non-HM group, HM group showed higher FC between mPFG and bilateral middle frontal gyrus (MFG), ANG, and MTG (all P<0.01). In addition, HM patients showed higher FC between PCC/(preCUN) and the right cerebellum, superior frontal gyrus (SFG), left preCUN, superior frontal gyrus (SFG), and medial orbital of the superior frontal gyrus (ORB supmed; all P<0.01). CONCLUSION: HM patients show different ALFFs and DMNs compared with non-HM subjects, which may imply the cognitive alterations related to HM.