Aim To observe the effect of angiotensin(1-7) (Ang(1-7)) on myocardial apoptosis, and investigate the underlying mechanism. Methods H9c2 cells were treated by isoproterenol (ISO) for 12 h to eastablish a model of apoptosis. Co-treatment of Ang(1-7) or PI3K inhibitor (LY294002) with ISO or ISO and Ang(1-7) for 12 h was performed to observe the influence on ISO-induced myocardial apoptosis. The cell growth state was observed under white light. MTS was used to detect the relative cellular activity. The apoptotic rate was tested by TUNEL under fluorescence microscope. The mitochondrial transmembrane potential was detected by fluorescence probe JC-1. The protein expression of cleaved Caspase-3, p-Akt and Akt were tested by Western blot. Results ISO inhibited the relative activity of H9c2 cells. Ang(1-7) reversed the ISO-induced cellular activity reduction of H9c2 cells concentration-dependently. Compared with control group, apoptosis rate and the protein expression of cleaved Caspase-3 increased significantly in ISO group, and the mitochondrial transmembrane potential and the protein expression of p-Akt decreased notably. Ang (1-7) could inhibit the increasing of apoptosic rate and the protein expression of cleaved Caspase-3, promote mitochondrial transmembrane potential and the protein expression of p-Akt in ISO-indcued H9c2 cell. The protective effect of Ang(1-7) on ISO-induced apoptosis was markedly reduced by pretreatment with LY294002, evidenced by increasing in apoptosic rate and the protein expression of cleaved Caspase-3, decreasing in the protein expression of p-Akt. Conclusion ISO induces apoptosis by decreasing mitochondrial transmembrane potential. Ang(1-7) could reverse this effect. Ang(1-7) protecting H9c2 cells from ISO-induced apoptosis may relate to PI3K/Akt signal pathway.