OBJECTIVE: During acute myocardial infarction (AMI), ferroptosis occurs in cardiomyocytes, leading to ventricular remodeling. To investigate the influence of exosomes (Exo) derived from adipose mesenchymal stem cells (AD-MSCs) on cardiomyocytes, a therapeutic approach to resolve AMI may be discovered. METHODS: The Exo of AD-MSCs was isolated and identified, and internalized into cardiomyocytes. RESULTS: Exo was isolated and identified successfully, and further confirmed that it could be internalized into H9C2 cells. Compared with the control group, the level of apoptosis and ferroptosis in OGD group was significantly increased, while the level of cell vitality was significantly decreased. After Exo treatment, the level of ferroptosis and apoptosis was significantly decreased, while the level of cell vitality was significantly increased. However, after overexpression of ATF3 in cells, it was found that the ferroptosis level down-regulated by Exo was reversed. Further examination of the SLC7A11/Xct system showed that ATF3 could inhibit the expression of SLC7A11. In addition, compared with the AMI+PBS group, the infarct size of the AMI+Exo group was significantly reduced, and the level of cardiomyocyte apoptosis and ferroptosis was also significantly improved. CONCLUSION: Exo derived from AD-MSCs can inhibit the expression of ATF3, promote the transport of Fe