Retinitis pigmentosa (RP) is a disorder that results in the death of rod photoreceptors in the retina, caused by several different mutations. As rods are 95 % of the photoreceptors in the eye and consume the most oxygen, their death causes tissue hyperoxia resulting in oxidative stress in the retina. Oxidative stress is implicated in the pathogenesis of photoreceptor death in RP. Therefore, oxidative stress models are very relevant to identifying drugs to prevent photoreceptor death in RP. Rabbits are an excellent model to study retinal degeneration due to their large eyes and therefore larger subretinal and vitreous space, makes it easier for surgical and drug interventions techniques. Herein, we have created a rabbit model of oxidative stress-induced retinal degeneration using paraquat (PQ), a known oxidant. PQ causes oxidative stress in the retina, that results in functional and structural loss of photoreceptors. We also show that using an antioxidant PEDF[H105A], we were able to blunt the damage to photoreceptors caused by PQ. Therefore, this rabbit model of oxidative stress-induced retinal degeneration will serve as an excellent model to test a wide array of surgical and drug interventions techniques.