Diabetic　retinopathy　(DR)　is　a　leading　cause　of　blindness　globally　and　its　pathogenesis　has　still　not　been　completely　elucidated.　Some　studies　show　a　close　relation　between　oxidative　stress　and　DR.　This　study　was　aimed　to　investigate　the　effects　of　anti-oxidant　in　DR　and　expression　of　vascular　endothelial　growth　factor　(VEGF)　and　intercellular　adhesion　molecule-1　(ICAM-1)　from　retinal　blood　vessels　in　diabetic　rats.　Diabetic　rat　models　were　established　by　intraperitoneal　injection　of　streptozotocin　(60　mg/kg)　and　confirmation　of　high　serum　glucose　levels　in　the　animals.　Antioxidant　N-acetylcysteine　was　given　to　diabetic　rats　to　elicit　antioxidative　responses,　and　rats　were　sacrificed　at　3　and　5　months.　Ultrastructures　of　retinal　vascular　tissues　were　observed　under　transmission　electron　microscope,　and　pathology　of　retinal　capillaries　was　examined　using　retinal　vascular　digest　preparations.　Changes　in　the　expression　of　VEGF　and　ICAM-1　were　examined　by　immunofluorescence;　and　reactive　oxygen　species　contents　in　the　retinas　were　detected　using　dichlorofluorescein　assay.　Compared　with　normal　rats,　diabetic　rats　displayed　significant　retinopathy　both　under　electronic　and　light　microscopy,　accompanied　by　elevated　reactive　oxygen　species　contents　in　the　retinas;　N-acetylcysteine　treatment　alleviated　the　pathological　changes　and　also　decreased　reactive　oxygen　species,　most　significantly　at　5　months.　VEGF　and　ICAM-1　expressions　were　significantly　up-regulated　in　retinal　blood　vessels　from　diabetic　rats,　and　such　up-regulation　was　attenuated　by　N-acetylcysteine　treatment.　The　expression　of　both　factors　returned　to　basal　levels　after　5-month　treatment　with　N-acetylcysteine.　Long-term　N-acetylcysteine　treatment　exerts　protective　effects　on　the　diabetic　retinas,　possibly　through　its　down-regulation　of　the　expression　of　VEGF　and　ICAM-1,　and　reduction　of　reactive　oxygen　species　content　in　retinal　vascular　tissues　in　diabetic　rats.