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Many reports have shown that Wnt/β-Catenin pathway is associated with a variety of diseases, but its role in the pathogenesis of myopia is still unknown. In order to clarify the role of Wnt/β-catenin pathway in the development of form deprivation myopia (FDM), this study investigated the expression of scleral Wls, β-catenin and TCF4 in mice model of form deprivation (FD) myopia. Three parallel experimental groups, including FD, monocular exposure (SC) and binocular exposure (NC) group, were designed to investigate the effects of Wnt/β-Catenin pathway on scleral remodeling mouse during form deprivation in three-week-old C57BL/6 mice. Diopters and axial lengths (AL) in each sample were measured with an infrared eccentric refractometer or spectral-domain optical coherence tomography. The expression of scleral Wls, β-catenin and TCF4 were detected with Western blot. Morphological changes of posterior sclera were observed with a transmission electron microscope (TEM). The above characterization and analysis were performed on the 0th, 7th, 14th, 21st and 28th days, respectively. The difference of diopter and AL between the three groups (SC, NC and FD group) gradually increased with the prolongation of FD time (except AL between SC and NC groups). The changes of diopter and AL gradually increased with the prolongation of FD time. Especially, the diopter and AL will increase sharply after FD lasts for a long time, such as the measurement on the 21st for diopter and 28th days for AL. Most notably, the AL of FD eyes significantly increased after 28 days of deprivation. Thinning and disordered arrangement of collagen fibers and a decrease of extracellular matrix were observed with TEM. The expression of scleral Wls, β-catenin and TCF4 increased with age in the NC and SC group. In FD group, they increased significantly on the 7th, 14th and 21st days but decreased on the 28th day. The expression of Wls, β-Catenin and TCF4 to FD were more sensitive indicators than that of diopter and AL. Within the first 7 days of FD, the expression of Wls, β-Catenin and TCF4 in sclera increased sharply. With the extension of FD duration, it gradually decreased. It is suggested that the Wnt/β-catenin pathway might be involved in the scleral remodeling induced in FDM mice.