Organophosphorus insecticide poisoning is widely investigated, and a growing number of evidence indicates its effects to cause ocular lesions, but the mechanisms of its ocular effects are not well elucidated. Here, effects of organophosphorus insecticide chlorpyrifos on mouse retina in vivo and protection of combination of vitamins C and E were reported. Cell apoptosis, lipid peroxidation and DNA damage were increased, and activities of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were decreased in retina of chlorpyrifos-administrated mice (63mg/kg, single treatment, via oral gavage). Pretreatment of combination of antioxidants vitamin C (250mg/kg) and vitamin E (150mg/kg) (once daily for 6 days, hypodermic injecting) significantly attenuated these effects of chlorpyrifos, demonstrating oxidative stress was involved in chlorpyrifos-induced cell apoptosis in mouse retina. Moreover, chlorpyrifos treatment inhibited acetylcholinesterase activity and promoted [Ca(2+)](i) level in mouse retinal cells, which were also attenuated by combination of vitamins C and E. These results may have implications for treatment of organophosphorus insecticide poisoning in retina with combination of vitamins C and E.