Collectively, the present study provides for the first time the new pharmacological effects that acacetin decreases the progression of myocarditis and cardiomyopathy via reducing mitochondrial complex II activity, thereby inhibiting mitochondrial respiration and mROS of CD4+ T cells, suggesting that acacetin may be a valuable therapeutic drug in CD4+ T cell-mediated myocarditis. Here, CD4 is linked to myocarditis.