Apoptosis following ischemia and reperfusion is a significant cause of cell death in cardiomyocytes. Protein Phosphatase 2a (PP2a) has previously been shown to activate proteins essential in the progression of apoptosis, and it was therefore hypothesized that inhibition of PP2a would result in decreased apoptosis following ischemia/reperfusion (I/R). To test this hypothesis, neonatal rat cardiomyocytes were subjected to simulated I/R and one of two PP2a inhibitors, fostriecin or okadaic acid, were administered at the onset of both the ischemia and reperfusion phases. Following I/R, apoptosis was measured using Hoechst staining and Caspase-3 immunofluorescence. At 10nm and 50nm, okadaic acid caused a marked increase in apoptosis. Alternatively, PP2a inhibition by fostriecin resulted in decreased apoptosis at 3muM. At a concentration of 2muM however, fostriecin was found to increase apoptosis following I/R. The results indicate that PP2a inhibition using fostriecin at some concentrations may be useful in attenuating apoptosis resulting from UR injury.