In this study, the effects of tea catechins and tea theaflavins on myocardial contraction were examined in isolated rat hearts using Langendorff-perfusion system. We found that both tea catechins and theaflavins had positive inotropic effects on the myocardium. Of the tested chemicals, epicatechin-3-gallate (ECG) and theaflavin-3,3’-digallate (TF4) appear to be the most effective tea catechin and theaflavin, respectively. Further studies of ECG-induced positive inotropy revealed the following insights: First, unlike digitalis drugs, ECG had no effect on intracellular Ca2+ in cultured adult cardiac myocytes. Second, it activated PKC, but not PKC, in the isolated hearts as well as in cultured cells. Neither a phospholipase C (PLC) inhibitor (U73122) nor antioxidant N-acetyl cysteine (NAC) affected the ECG-induced activation of PKC . Third, inhibition of PKC by either chelerythrine chloride (CHE) or PKC translocation inhibitor peptide (TIP) caused a partial reduction of ECG-induced increases in myocardial contraction. Moreover, NAC was also effective in reducing the effects of ECG on myocardial contraction. Finally, pretreatment of the heart with both CHE and NAC completely abolished ECG-induced inotropic effects on the heart. Taken together, these findings indicate that ECG can regulate myocardial contractility via a novel PKC -dependent signaling pathway.