Myopia has become a worldwide public health problem. In this study, we constructed a form deprivation (FD) myopia mouse model and explored the potential role of NF-kappa B pathway and inflammatory cytokines in scleral remodeling during myopia development. Wild-type (WT) mice and C6-knockout (KO) mice were categorized into two groups: FD and normal control (NC). The right eye was covered using a translucent balloon for 4 weeks, and the left eye remained untreated which served as self-control. NC group received no treatment. Refractive error and axial length were measured at baseline, 2 weeks, 4 weeks later under normal visual conditions, and 4 weeks after FD. The mRNA and protein levels of scleral TNF-alpha, IL-6, IL-1 beta, MMP-2, collagen I, and p-NF-kappa B p65 were detected using quantitative PCR and western blot. Under normal visual conditions, no significant difference existed in refraction and axial length between WT and C6 KO mice. After 4 weeks of deprivation, the interocular differences of C6 KO mice were lower than those of WT mice (refraction - 2.41 +/- 0.86D vs. - 4.33 +/- 0.87D, P = 0.003; axial length 0.044 +/- 0.028 mm vs. 0.082 +/- 0.026 mm, P = 0.034). Moreover, TNF-alpha, IL-6, IL-1 beta, MMP-2, and p-NF-kappa B p65 levels increased, and collagen I levels decreased in deprived eyes of WT mice. Whereas these trends were weakened in C6 KO mice. Scleral C5b-9 could activate the NF-kappa B pathway, promoting the expression of inflammatory cytokines and MMP-2 levels, which ultimately affected scleral remodeling.