Epithelial-mesenchymal transition (EMT) is an important mechanism of cardiac fibrosis after myocardial infarction (MI). However, it remains unclear whether Snail1, an important regulator of EMT, is involved in cardiac fibrosis. In this study, we explored the expression patterns of Snail1 and a cardiac fibrosis marker-periostin-after MI in mice and then investigated the co-expression between Snail1 and periostin after MI in mice. Our results showed that the mRNA and protein levels of Snail1 and periostin were significantly increased in the infarct area. The Snail1 expression pattern appeared to be parabolic within 14 days after MI. In addition, after MI, all Snail1-positive cells were able to express periostin. These results indicate that Snail1 is mainly activated in the infarct area and is involved in de novo cardiac fibrosis after MI in mice. Thus, it is a potential molecular target in the development of drug interventions for ventricular remodeling after MI.