To investigate the effects of total flavones of Abelmoschus manihot(TFA) on myocardial ischemia-reperfusion injury in elderly diabetic rats and reveal the potential mechanism.Methods:The simple random method was used to assign elderly rats into sham(threading without ligature)，model(diabetic myocardial ischemia-reperfusion)，low-and high-dose(75 and 150 mg/kg，respectively) TFA，inhibitor [10 mg/kg nuclear factor κB(NF-κB) inhibitor BAY11-7082]，and high-dose TFA+inhibitor(150 mg/kg TFA+10 mg/kg BAY11-7082) groups.The cardiac function indicators，myocardial infarction area，serum levels of indicators，apoptosis rate of myocardial cells，and expression of related proteins in the myocardial tissue were observed and compared.Results:Compared with the model group，the low-and high-dose TFA，inhibitor，and high-dose TFA+inhibitor groups showed reduced myocardial infarction area，lowered levels of cardiac troponin T(cTnT)，creatine kinase isoenzyme MB(CK-MB)，lactate dehydrogenase(LDH)，and malondialdehyde(MDA)，decreased positive rate of TdT-mediated dUDP nick end labeling(Tunel)，and downregulated protein levels of phosphorylated NF-κB p65(P-NF-κB p65)，cleaved cysteine aspartate proteinase-3(Cl-caspase-3) and B-cell lymphoma 2(Bcl-2)-associated X protein(Bax)(all P<0.05).Meanwhile，these groups showcased increased left ventricular ejection fraction(LVEF) and upregulated protein levels of nuclear factor κB inhibitory protein(IκBα) and Bcl-2(all P<0.05).Compared with the high-dose TFA group，the high-dose TFA+inhibitor group presented decreased myocardial infarction area，lowered levels of cTnT，CK-MB，LDH，and MDA，reduced Tunel positive cell rate，downregulated protein levels of p-NF-κB p65，Cl-caspase-3，and Bax(all P<0.05)，increased LVEF，and upregulated protein levels of IκBα and Bcl-2(all P<0.05).Conclusion:TFA may inhibit myocardial apoptosis and oxidative stress and improve the cardiac function in elderly diabetic rats with myocardial ischemia-reperfusion by regulating the NF-κB signaling pathway.