Our animal experimental study found that the FGF21/FGFR1/PI3K/AKT pathway was activated, and the oxidative stress and the expression of ER stress-related apoptosis proteins such as IREα, JNK, GRP78, CHOP, c-caspase3, Bax/Bcl-2 were significantly increased in the heart of post-MI mice, whereas the phenomenon was reversed by aerobic exercise. Here, FGF21 is linked to myocardial infarction.