In this study, we found that knocking down the expression of S100A1 significantly attenuated the effects of reynoutrin on improving cardiac function, cardiomyocytes apoptosis, myocardial inflammation and fibrosis, and down-regulating the expressions of MMP2, MMP9, p-p65, and TGF-β1 in rats with IHF. The gene discussed is MMP2; the disease is myocarditis.