〔Abstract〕 Objective To investigate the effect of overexpression of a disintegrin and metalloproteinase 10(ADAM10) on myocardial cell apoptosis and Notch/Akt signaling pathway in acute myocardial infarction(AMI) rats. Methods A total of forty SD rats were randomly divided into four groups:sham operation group(sham), acute myocardial infarction group(AMI), empty adenovirus group(Ad-NC) and ADAM10 adenovirus group(Ad-ADAM10), with 10 rats in each group. Except for the sham group, the other groups were ligated the left anterior descending branch of coronary artery to establish the AMI models, and adenovirus was injected to the myocardial infarction area in situ. Cardiac function was detected by cardiac ultrasound after 72 h of intervention. Myocardial tissue was taken and TCC staining was used to evaluate myocardial infarction area. TUNEL staining was used to detect myocardial cell apoptosis. ADAM10 mRNA expression level in myocardial tissue was detected by RT-PCR. The expression levels of ADAM10, apoptosis-related proteins and Notch/Akt signaling proteins were detected by Western blot. Results Compared with sham group, the cardiac function in the AMI group decreased(P<0.05), myocardial infarct size and myocardial apoptosis rate increased(P<0.05), the mRNA and protein expression of ADAM10 and the protein expression levels of Bcl-2, Notch1, Hes1 and p-Akt decreased(P<0.05), while the protein expression levels of Cleaved-caspased-3 and Bax increased(P<0.05). Compared with AMI group, the cardiac function of rats in Ad-ADAM10 group improved(P<0.05), myocardial infarct size and myocardial apoptosis rate decreased(P<0.05), the mRNA and protein levels of ADAM10 in myocardial tissue and the protein expression of Bcl-2, Notch1, Hes1, p-Akt increased(P<0.05), while the protein expression levels of Cleaved-caspase-3 and Bax decreased(P<0.05). However, there was no significant difference between the above indexes in Ad-NC group and AMI group(P>0.05). Conclusion Overexpression of ADAM10 can improve cardiac function and inhibit cardiomyocyte apoptosis in AMI rats, and its mechanism may be related to the activation of Notch/Akt signaling pathway.