Pathophysiological mechanisms correlating diabetes mellitus with associated complications are still not completely clear, even though oxidative stress seems to play a pivotal role. Literature data suggest that cell damages induced by hyperglycemia, although multifactorial, have a common pathway in oxidative/nitrosative stress. The present study evaluated the effects of Betula etnensis Raf. bark extract, a plant belonging to the Betulaceae family endemic to Sicily, on oxidative stress and in preventing and/or retarding diabetes-associated complications in streptozotocin diabetic rats treated with the extract at dose of 0.5 g/kg body weight per day for 28 consecutive days. The extract administration significant decreased food and water intake, fasting blood glucose, weight loss and polyuria, compared with untreated diabetic animals. Furthermore, oxidative stress markers particularly, lipid hydroperoxides (LOOH) and nitrite/nitrate levels, non-proteic thiol groups (RSH), γ-glutamyl-cysteine-synthetase (γ-GCS) activities and expression, heme oxygenase-1 (HO-1), endothelial and inducible nitric oxide synthases (i-NOS e-NOS) expression, significantly changed by streptozocin treatment, were markedly restored both in plasma and tissues together with nuclear sirtuins activity (Sirt1). Results suggested that B. etnensis bark alcoholic extract is able to counteract oxidative stress and to ameliorate some general parameters related to diabetes.