〔Abstract〕 Objective This study aims to investigate the effects of imperatorin on myocardial injury and oxidative stress in myocardial ischemia-reperfusion rats by inhibiting the activation of extracellular signal-regulated kinase 1/2(ERK1/2)and Nuclear factor-kappaB phosphorylation-65(NF-kappaB p65).Methods SD rats were randomly divided into five groups:healthy Control group(Control group),myocardial ischemia-reperfusion model group(MI/R group),and low,medium and high doses of imperatorin 6.25,12.5 and 25 mg/kg groups.The rat heart rate(HR) and left ventricular shortening fraction score(FS) were detected by small animal ultrasound instrument.Enzyme-linked immunosorbent assay(ELISA) was used to detect creatine kinase-MB(CK-MB)and Cardiac troponin I(cTnI).Myocardial tissue damage was observed by HE staining.Terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labelling(TUNEL) was used to detect the apoptosis of cardiomyocytes.The expression of apoptosis-related proteins Bax,Bcl-2,Caspase-3 and pathway proteins ERK1/2 and NF-κB p65 were detected by Western blot. Superoxide dismutase( SOD) activity and Malondialdehyde( MDA) content were detected by the kit.Results Compared with the control group,HR and FS in MI/R group significantly reduced( P<0. 05); CK-MB and cTnI concentrations increased significantly( P<0. 05); myocardial tissue damage was obvious; apoptotic cells and Bax/Bcl-2 expression ratio significantly increased( P<0. 05); SOD activity significantly decreased( P<0. 05),while MDA content significantly increased( P<0. 05); phosphorylation of ERK1/2 and NF-κB p65 significantly increased( P<0. 05). The above results were reversed in MI/R rats after administration of imperatorin. Compared with the MI/R group,the HR and FS of the medium and high doses imperatorin groups were significantly recovered( P<0. 05); the concentration of CK-MB and cTnI decreased significantly( P<0. 05); myocardial tissue injury improved obviously; apoptotic cells and Bax/Bcl-2 expression ratio decreased significantly( P<0. 05); SOD activity significantly increased( P<0. 05),while MDA content significantly decreased( P<0. 05); phosphorylation of ERK1/2 and NF-κB p65 decreased significantly( P<0. 05). Conclusion Imperatorin can alleviate myocardial injury and oxidative stress in MI/R rats by inhibiting the activation of ERK1/2 and NF-κB p65 pathway proteins.