Ultrafine Particulate Matter (UFP) has been associated with increased cardiovascular morbidity and mortality. However, the mechanisms that drive PM associated cardiovascular disease and dysfunction remain unclear. We examined the impact of oropharyngeal aspiration of 100 μg UFP from the Chapel Hill, NC air shed in Sprague-Dawley rats on cardiac function, arrhythmogenesis, and cardiac ischemia/reperfusion (I/R) injury using a Langendorff working heart model. We found that exposure to UFP was capable of significantly exacerbating cardiac I/R injury without changes to overall cardiac function or major changes in arrhythmogenesis. Cardiac I/R injury was attenuable with administration of Cyclosporin A (CsA), suggesting a role for the mitochondrial permeability transition pore (mPTP) in UFP associated cardiovascular toxicity. Isolated cardiac mitochondria displayed decreased Ca2+ buffering before opening of the mPTP. These findings suggest that UFP induced expansion of cardiac I/R injury may be a result of mPTP Ca2+ sensitization resulting in increased mitochondrial permeability transition and potential initiation of mPTP associated cell death pathways.