Photoreceptor degeneration (PD) refers to a group of heterogeneous outer retinal dystrophies characterized by the death of photoreceptors. Both oxidative stress and inflammation are involved in the pathogenesis of PD. We investigate whether vitamin D has a potential for the treatment of PD by evaluating the anti-oxidative stress and anti-inflammatory properties of the active form of vitamin D3, 1,α, 25-dihydroxyvitamin D3, in a mouse cone cell line, 661W. Mouse cone cells were treated with H2O2 or a mixture of H2O2 and vitamin D; cell viability was determined. The production of reactive oxygen species (ROS) in treated and untreated cells was measured. The expression of key anti-oxidative stress and inflammatory genes in treated and untreated cells was determined. Treatment with vitamin D significantly increased cell viability and decreased ROS production in 661W cells under oxidative stress induced by H2O2. H2O2 treatment in 661W cells can significantly down-regulate the expression of antioxidant genes and up-regulate the expression of neurotoxic cytokines. Vitamin D treatment significantly reversed these effects and restored the expression of antioxidant genes. Vitamin D treatment also can block H2O2 induced oxidative damages. The data suggested that vitamin D may offer a therapeutic potential for patients with PD.