To explore whether the ameliorative effect of swimming exercise pretreatment is dependent on the effect of SIRT2 on mitochondrial biogenesis‐related proteins, we delivered a SIRT2‐specific inhibitor, AGK2 (IC50 = 3.5 μM), via stereotactic injections into the CA1 hippocampal brain of T2DM rats to downregulate SIRT2 following swimming exercise. The gene discussed is SIRT2; the disease is type 2 diabetes mellitus.