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Background: To investigate structural and functional changes of brain in children with intermittent exotropia (IXT) and their relationship with clinical features. Methods: Twenty-one IXT patients (mean age 9.38 ± 2.62 years) and 21 age-, gender-, education-, and handedness-matched healthy controls (HCs, mean age 9.52 ± 3.28 years) underwent high-resolution T1 imaging, diffusion tensor imaging (DTI), and resting-state functional MRI (rs-fMRI). The gray and white matter volume analyzed by voxel-based morphometry (VBM) based on T1 imaging, the fractional anisotropy (FA) and mean diffusivity (MD) indices based on DTI, and the amplitude of low frequency fluctuation (ALFF) value based on rs-fMRI were compared between these 2 groups. The correlations between MRI-derived parameters in significant brain regions and various clinical characteristics of IXT were analyzed. Results: Compared with HCs, IXT children showed significantly decreased FA in right precentral gyrus (PRG) and right postcentral gyrus (POG), and significantly decreased ALFF in bilateral calcarine sulcus, bilateral cuneus, left lingual gyrus, and left superior occipital gyrus. The FA value in right PRG and right POG was negatively correlated with disease duration (r = 20.520, P = 0.016), angle of exodeviation at near (r = 20.549, P = 0.010), and angle of exodeviation at distance (r = 20.547, P = 0.010). Conclusions: IXT children exhibited abnormalities of white matter microstructure and reduced spontaneous neural activities in brain regions involving in oculomotor performance and binocular fusion. Further studies are needed to determine whether these findings are related to the neuropathologic mechanism or downstream changes of IXT. [ABSTRACT FROM AUTHOR]