In the present paper the anti-diabetic effects of stem-bark extract (ethanol 70%) of Vatairea macrocarpa, a traditional diabetes mellitus treatment widely used in Brazil, are reported. The extract was administered orally at a dose of 250 or 500 mg/kg, for 22 days, to normal and streptozotocin-diabetic rats. In extract treated (500 mg/kg) diabetic rats serum and urinary glucose, urinary urea, food and fluid intake were decreased, while body weight gain was increased, all of which indicate an improvement in diabetic state ( p < 0.05). No effects of the extract were observed in non-diabetic rats. In extract treated (500 mg/kg) diabetic group HOMA-R (homeostasis model for assessment of insulin resistance) was lower at the end of 22 days, as compared to diabetic non treated control group. Insulin was the reference substance used in the experiments. In an oral glucose tolerance test, the time to reach maximal glycemia was greater in diabetic 500 mg/kg treated group than in control group. These anti-diabetic effects could be related to an improved insulin resistance, although a possible effect on pancreatic B-cell function cannot be excluded. Thus, our data of sub-chronic experiments suggest that long-term use of V. macrocarpa stem-bark extract may be helpful in treating diabetic conditions.