〔Abstract〕 Objective To analyze the effects of miR-346 on alleviating cardiac function damage and oxidative stress in rats undergoing myocardial ischemia/reperfusion(I/R).Methods A total of 48 rats were randomly divided into control group, I/R group, I/R+agomiR-NC group and I/R+agomiR-346 group. I/R model was replicated by the ligation of left anterior descending coronary artery. The recombinant adeno-associated virus miR-346 was injected through the tail vein for overexpression intervention. After 120 minutes of reperfusion, heart rate(HR), left ventricular ejection fraction(LVEF), fractional shortening(FS) and left ventricular wall thickness(LVWT), levels of serum creatine kinase MB(CK-MB), myoglobin(Mb), lactate dehydrogenase(LDH) and cardiac troponin I (cTnI), and levels of superoxide dismutase( SOD), glutathion peroxidase( GSH-Px) and malondialdehyde(MDA) in myocardial tissues were detected. The apoptosis of myocardial tissue cells was detected by TUNEL staining. The expression of B-cell lymphoma/leukemia-2(Bcl-2) gene, Bcl-associated x protein(Bax), cysteine protease 3( Cas-3) and Cas-9 in myocardial tissues was detected by Western blot.Results HR, LVEF, FS and LVWT in I/R group were lower than those in control group, the levels of serum CK-MB, LDH, Mb and cTnI were higher than those in control group, the expression of MDA, Bax/Bcl-2, cleaved Cas-3/Cas-3 and cleaved Cas-9/Cas-9 proteins in myocardial tissues was higher than that in control group, the levels of SOD and GSH-px were lower than those in control group, and the apoptosis rate of myocardial tissue cells was higher than that in control group(P<0. 05). HR, LVEF, FS and LVWT in I/R + agomiR-346 group were higher than those in I/R + agomiR-NC group, the levels of serum CK-MB, LDH, Mb and cTnI were lower than those in I/R + agomiR-NC group, the expression of MDA, Bax/Bcl-2, cleaved Cas-3/Cas-3 and cleaved Cas-9/Cas-9 proteins in myocardial tissues was lower than that in I/R + agomiR-NC group, the levels of SOD and GSH-px were higher than those in I/R + agomiRNC group, and the apoptosis rate of myocardial tissue cells was lower than that in I/R + agomiR-NC group(P<0. 05).Conclusion The miR-346 overexpression can reduce oxidative stress level in I/R rats, alleviate myocardial tissue damage, and improve cardiac function.