Aim To explore the roles of silent information regulator 1 （Sirt1） in edaravone （EDA）-induced myocardial protection in isoprenaline （ISO）-damaged H9c2 cardiomyocytes. Methods H9c2 cardiomyocytes were treated with ISO to establish an in vitro model of myocardial injury induced by persistent beta-1 adrenergic receptor excitement. Prior to the treatment with ISO, EDA was administered to test its protection. To clarify the roles of Sirt1, a selective inhibitor Sirtinol was used before ISO or EDA. Cell viability, lactate dehydrogenase （LDH） release, intracellular malondialdehyde （MDA） content, Sirt1 protein and glucose-regulated protein （GPR78） （an endoplasmic reticulum stress protein） expressions were measured. Results Treatment with ISO reduced viability and Sirt1 expression, raised LDH release from H9c2 cardiomyocytes. Preconditioning with 20 μmol/L Sirtinol for 30 min significantly attenuated the cell injury induced by treatment with 80 μmol/L ISO for 48 h （P<0.01）. Preconditioning with 40 μmol/L EDA partially decreased ISO-induced downregulation of Sirt1 （P<0.01）. In addition, pretreatment with EDA exhibited obvious cardiac protection, evidenced by increased viability （P<0.01）, suppressed LDH release （P<0.01）, MDA generation （P<0.01） and GRP78 expression （P<0.01）. These protective effects were markedly impeded by pretreatment with 20 μmol/L Sirtinol for 30 min. Conclusion Sirt1 participates in EDA-induced myocardial protection against ISO-caused injury in H9c2 cardiomyocytes.