Objective Tea is the most consumed beverage in the world. (-)-Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, is effective in the prevention of several chronic diseases, and is marketed as part of many dietary supplements. We have now examined the myocardiotoxic effect of high doses of EGCG in mice. Results EGCG (500 and 1000 mg/kg center dot d) induced cardiac collagen synthesis and fibrosis-related protein expression, such as connective tissue growth factor (CTGF) and fibronectin (FN) in mice. Moreover, EGCG decreased the protein expression of p-AMPK and increased the levels of p-p70S6 K and p-S6. Conclusion This is the first evidence that high oral doses of EGCG could induce cardiac fibrosis, and shed new light on the understanding of EGCG-mediated myocardiotoxicity.