Moderate alcohol or red wine consumption reduces the risk of cardiovascular mortality. This cardiovascular protection is likely due to the additive, combined and/or synergistic effects of alcohol itself or other components of wine, in particular polyphenols. Experiments were carried out to determine whether ethanol/polyphenols also decrease plasminogen activator inhibitor type 1 (PAI-1) mRNA expression in vivo, using the rat as an animal model. Male Sprague-Dawley rats were gavaged with ethanol, the individual polyphenols catechin and quercetin or saline vehicle. The in vivo effect of ethanol or individual polyphenols on PAI-1 mRNA was then assessed by in situ hybridisation and quantitative reverse transcriptase (RT) polymerase chain reaction (RT-PCR). PAI-1 mRNA expression was significantly reduced in the endothelial and smooth muscle cells of the thoracic aorta of all experimental rats. RT-PCR analysis of PAI-1 mRNA levels in vascular tissue showed a ∼55% reduction in PAI-1 mRNA consistent with the decrease in aortic endothelium PAI-1 mRNA observed with in situ hybridisation. This decrease may enhance endothelial cell (EC)-mediated fibrinolytic activity in vivo. The cardioprotection afforded by moderate red wine consumption can therefore be attributed in part to the combined effects of ethanol and individual polyphenols on EC fibrinolysis.