Myocardial ischemia (MI) is a common disease with high mortality and morbidity worldwide. Since the pathological process of MI is very complicated, a comprehensive understanding of its pathogenesis is the key to the treatment of MI. As chromatin plays a crucial role in regulating gene expression, and gene regulation is a fundamental process in developing and disease progression, combined analysis of the chromatin and gene can further reveal the pathological mechanism of MI. In this study, Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) was used to identified open chromatin, RNA-seq was applied to detected differential expression profiling. The combined analysis of ATAC-seq and RNA-seq showed that inflammatory response was critical in MI injury. Analysis of transcription factors (TFs) found a key TF, STAT2 (signal transducers and activators of transcription 2). The annotation analysis of target genes predicted by Stat2 found most of these genes were involved in inflammation, which indicated Stat2 was a key regulator of inflammatory response after MI. This study reveals a deeper regulatory mechanism of inflammation after MI from the levels of chromatin, TFs, and genes; Stat2 may be the core of this regulator network. These results provide a more specific target for early intervention of inflammation after MI.