Abstract： Objective： To investigate the curative effect of Yiqi Zhenxin （YQZX） Decoction on H2O2-induced mitochondrial injury in H9c2 cardiocyte and its mechanism. Methods： A H2O2-induced cardiocyte injury model was established and divided into nine groups （n=5） as follows： the normal group （H2O2-free treatment）， the model group （H2O2-treated H9c2 cardiocyte）， the high-dose YQZX group [3.5 g（/ kg·d）]，the medium-dose YQZX group [1.2 g（/ kg·d）]，the low-dose YQZX group [0.4 g（/ kg·d）]，the high-dose YQZX+phosphoinositide 3-kinase （PI3K） inhibitor（ LY294002） group，the high-dose YQZX+cysclic guanosine monophosphate（ cGMP） inhibitor（ ODQ） group， the high-dose YQZX + protein kinaseCε2 （PKCε2） inhibitor （Epsilon-V1-2） group， and the high-dose YQZX+ mitochondrial permeability transition pore （mPTP） opener （Atractyloside） group. Cell viability was measured using the cell counting kit-8 （CCK-8） assay， cGMP expression was detected by the enzyme-linked immunosorbent assay （ELISA），and expression levels of PI3K，AKT，and PKCε2 mRNA were detected by the reverse transcriptionpolymerase chain reaction （RT-PCR）， and protein levels of phosphorylated PI3K （p-PI3K）/PI3K， p-AKT/AKT， and PKCε2 were analyzed by the Western blot. Results：Compared with the normal group，the model group showed a decreasing trend in cardiocyte viability， cGMP expression， expression levels of PI3K， AKT， and PKCε2 mRNA， and protein levels of p-PI3K/PI3K，p-AKT/AKT and p-PKCε2/PKCε2 （P＜0.05）；compared with the model group， the high-dose YQZX group presented an increasing trend in cardiocyte viability，cGMP expression，expression levels of PI3K， AKT， and PKCε2 mRNA， and protein levels of p-PI3K/PI3K， p-AKT/AKT and p-PKCε2/PKCε2 （P＜ 0.05）； the protective effects of YQZX medicated serum were reversed to varying degrees in the high-dose YQZX + LY294002 group，the high-dose YQZX + ODQ group，the high-dose YQZX + Epsilon-V1-2 group，and the high-dose YQZX + Atractyloside group（P＜0.05）. Conclusion： YQZX exerts a significant protective effect on H2O2-induced mitochondrial injury in H9c2 cardiocyte， whose mechanism is related to the regulation of mRNA and protein phosphorylation expression related to PKCε2 and PI3K/AKT signaling pathway，and the inhibition of mPTP opener.