In the present study, we detected ferroptosis both in HG-treated H9C2 cells and in cardiac tissue of T1DM mice about 2 months after the onset of diabetes, as characterized by elevated Fe2+ content and lipid peroxidation levels, and decreased GSH levels and SLC7A11/GPX4 expressions, which were recovered by irisin treatment. Here, GPX4 is linked to type 1 diabetes mellitus.