Myopia is an abnormal vision condition characterized by difficulties in seeing distant objects. Myopia has become a public health issue not only in Asian countries but also in Western countries. Previously, we found that violet light (VL, 360-400?nm wavelength) exposure effectively suppressed myopia progression in experimental chick and mice models of myopia. The inhibitory effects of VL on myopia progression are reduced in retina-specific opsin 5 (Opn5) knockout (KO) mice. Furthermore, VL exposure upregulated early growth response-1 (Egr-1) expression in the chorioretinal tissues of chicks. However, the expression of EGR-1 and role of OPN5 in mice following VL exposure remain unclear. In this study, we examined whether VL exposure-induced EGR-1 upregulation depends on Opn5 expression in the mouse retina. EGR-1 mRNA and protein expressions increased in the mouse retina and mouse retinal 661W cells following VL exposure. These increases were consistently reduced in retina specific Opn5 conditional KO mice and Opn5 KO 661W cells. Our results suggest that OPN5 mediates VL-induced EGR-1 upregulation in mice. These molecular targets could be considered for the prevention and treatment of myopia.