Objective and design: We tested here the effects of acute administration of an oxygen/ozone (O-3) mixture on the myocardial tissue damage following an ischemic event. Material or subjects: The study was done in Sprague-Dawley rats subjected to acute myocardial ischemia/reperfusion (I/R). Treatment: 100; 150; and 300 mu g/kg oxygen/O-3 mixture were insufflated intraperitoneally 1 h prior to I/R. Methods: Myocardial infarct size measurement and immunhistochemistry or ELISA for nitrotyrosine, CD68, CD8, CD4 and caspase-3 were done. Results: I/R produced a marked damage in the rat left ventricle with an infarct size as percentage of the area at risk (IS/AR) of similar to 45 +/- 4%. Rats insufflated with a oxygen/O-3 mixture showed a significant 2-h cardio-protection (e. g. infarct size over area at risk for the dose of 300 mu g/kg was similar to 30 +/- 3%,) as compared with control rats (P < 0.01). This effect was paralleled by a decrease in tissue levels of immunostaining for biomarkers of nitrosative stress (nitrotyrosine), inflammation (CD68) and immunity response (CD8 and CD4) between heart tissues from infarcted rats and infarcted 03 treated rats. Conclusions: These data indicate that the tissue and biochemical damages associated with myocardial ischemia/reperfusion can be counteracted by an acute 03 pretreatment.