Herein, we established an STZ-induced DM model in myocardial I/R rats and an H/R (hypoxia/reoxygenation) injury model in H9C2 cells under HG (high glucose)/NG (normal glucose) condition; examined the changes in the β2AR, cAMP/PKA, and BDNF/TrkB signaling pathways; and investigated whether Caveolin-3 improves the repair of H/R injury and I/R injury in vitro and in vivo, respectively, through the β2AR, cAMP/PKA, and BDNF/TrkB signaling pathways. This evidence concerns the gene CAV3 and diabetes mellitus.