Dietary fiber (DF) and resistant starch (RS) in the grains of cereals are fermented into short chain fatty acids (SCFA), including butyrate, propionate, and acetate, in the large intestine, and are absorbed into the blood. Effectiveness of SCFA in reducing myocardial damage was evaluated in a rat model of 30 min ischemia and 3 h reperfusion with administration of SCFA (10 mg/kg) by peritoneal injection 1 h before occlusion. Butyrate and propionate significantly attenuated infarct size, an indicator of myocardial damage, when assessed by 2,3,5-triphenyltetrazolium chloride staining, reduced apoptosis in terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, and increased Bcl-2/Bax ratio, a determinant of cell survival in the apoptotic pathway. In addition, butyrate significantly attenuated the level of caspase-3, an executioner caspase, in an immunohistochemical assay. These results demonstrate that butyrate and propionate, produced by fermentation of DF and RS in the large intestine, could prevent myocardial infarction by attenuating apoptosis, possibly through inhibition of histone deacetylases. Thus, varieties of cereals or diets that produce a large amount of butyrate and propionate by fermentation could be beneficial in reducing myocardial infarction.