AIM:To explore the mechanism of α-lipoic acid(α-LA)on the protection of diabetic retinopathy. METHODS:The streptozotocin(45mg/kg)was intrape-ritoneally injected to establish the diabetic model in 16 male SD rats as experimental group,model rats were divided into diabetes group and α-lipoic acid(α-LA) group,control group also was established. α-lipoic acid was given to treatment group at dose of 100mg/(kg·d) by gavage. At 12 weeks, the blood glucose, content of malondialdehyde (MDA) and reduced glutathione hormone (GSH), the activity of superoxide dismutase(SOD) were assayed. Retinal capillary trypsin digestion were prepared to observe the changes of capillary vessel. The immunohistochemistry was used to assess the expression of NF-κB protein in retina. RESULTS:Compared with control group, the content of MDA, SOD and activity of GSH in diabetes group were significantly lower(P<0.05) . The number of pericytes and epithlium cells decreased obviously and cell-free capillary increased(P<0.05).The expression of NF-κB enhanced. Compared with diabetes group, the content of MDA decreased obviously while the content of SOD and activity of GSH increased significantly(P<0.05) in α-lipoic acid group. The number of pericytes and epithlium cells increased and cell-free capillary decreased obviously(P<0.05). The expression of NF-κB attenuated(P<0.01). CONCLUSION:The α-lipoic acid could inhibit the oxidative damage and activation of NF-κB and protect against diabetic retinopathy.