The effects of short- versus long-term alpha tocopherol administration on oxidative stress and survival of dorsal random flaps were studied in diabetic rats. Seven groups, with 20 rats in each, were constructed: (1) control, (2) noncontrolled diabetes, (3) noncontrolled diabetes+short-term a tocopherol, (4) noncontrolled diabetes +long-term alpha tocopherol, (5) insulin treatment, (6) insulin +short-term alpha tocopherol, and (7) insulin+long-term a tocopherol. After 3 months of diabetes, dorsal McFarlane flaps were raised. Flap viability and free-radical measurements with histopathological examination were investigated. Mean flap survival in Groups I to VII were 84.0 +/- 2.2%, 55.0 +/- 2.4%, 57.0 +/- 2.5%. 57.8 +/- 3.7%, 64.1 +/- 4.1%, 70.0 +/- 4.9%, and 77.0 +/- 6,6%, respectively. Free-radical concentration, as assessed with luminol-and lucigenin-enhanced chemiluminiscence, was inversely correlated with flap survival. The results for viability and free-radical concentrations were significant between Groups 1, 2, 5, 6, and 7. Random flaps in diabetic animals showed significantly greater necrosis compared with controls. Among the diabetic animals, group receiving combination of insulin and long-term a tocopherol treatment had the greatest flap viability and least tissue free-radical concentration. Histopathological studies showed a hyalinization of arterioles in diabetics with long-term a tocopherol treatment protecting the vessel wall. In conclusion, random flaps in experimental diabetes mellitus show greater tissue oxidative stress and necrosis, which is only partially corrected with insulin treatment. Long-term antioxidant supplementation as an adjunct to insulin further lowers the oxidative stress, protects vessel structure and function, and therefore increases flap survival. (C) 2004 Elsevier Inc. All rights reserved.