Abstract: Objective To study the role of P53 in high glucose-induced apoptosis of cardiac muscle cells. Methods Cardiac muscle cells from SD rats were cultured and randomly divided into control group,P53 inhibitor（pifithrin-α） group（with a glucose concentration of 5.5mmol/L and a concentration of 50μmol/L）,high glucose（25mmol/L） group,and high+ pifithrinα（50μmol/L） group.Viability and apoptosis of cardiac muscle cells were detected by MTT assay and flow cytometry,respectively.Expression levels of P53,Bax and caspase-3 in cardiac muscle cells were measured by Western blot. Results The viability of cardiac muscle cells was significantly lower,the apoptosis rate of cardiac muscle cells was significantly higher,and the expression levels of P53,Bax and caspase-3 in cardiac muscle cells were significantly higher in high glucose group and high+ pifithrin-α group than in control group and P53 inhibitor group（P＜0.05）.The viability of cardiac muscle cells was significantly higher,the apoptosis rate of cardiac muscle cells was significantly lower,and the expression levels of P53,Bax and caspase-3 in cardiac muscle cells were significantly lower in high glucose + pifithrin-α group than in high glucose group（P＜0.05）. Conclusion High glucose can induce apoptosis of cardiac muscle cells by mediating transposition of P53 to mitochondria-activated apoptosis pathway.