In this study, we found that ACE2 overexpression prohibited downregulation of AMPK and PI3K/AKT signaling pathways by doxorubicin, indicating that AMPK and PI3K/AKT signaling pathways activated by ACE2 overexpression may play an important cardioprotective effect on doxorubicin-induced cardiomyopathy. Here, ACE2 is linked to cardiomyopathy.