Long-term consumption of red wine (RW) apparently confers some protection against cardiovascular diseases due to antiatherosclerotic properties of polyphenols and ethanol (EtOH). There is some evidence indicating that they do so by regulating angiogenesis, but the mechanism and the modulator factors involved are largely unknown. The aim of this study was to evaluate the effects of chronic ingestion of RW in vascular structure and in the pattern of expression of vascular growth factors in the rat corpus cavernosum. Male Wistar rats aged 6 mo were treated with RW or an equivalent EtOH solution, as the only liquid source for 6 mo. Expression of vascular endothelial growth factor (VEGF), angiopoietin 1 and angiopoietin 2, and their receptors (VEGFR1, VEGFR2, and Tie2) in cavernous tissue was assayed by immunofluorescence and Western blotting. A reduction of VEGF and VEGFR2 expression, respectively, in smooth muscle and endothelial cells was observed in RW-treated animals, which was balanced by an increase in angiopoietins/Tie2 expression. In EtOH rats, only a decrease in expression of the receptors VEGFR2 and Tie2 was observed. These results, taken together, suggest that antioxidants present in RW activate selected mechanisms for the maintenance of cavernous tissue vascularization. However, functional studies will be necessary to elucidate if RW is of benefit in the prevention of deleterious vascular events associated with ED.