Abstract: Extracellular matrix (ECM) is the main pathological product during fibrogenesis in ischemic myocardium after myocardial infarction. The progression and reconstruction rules of ECM develop along with different periods of the disease: in the inflammatory stage. A temporary matrix network forms with the degradation of original collagen matrix. In the proliferative stage, the enrichment of matricellular proteins activates myofibroblasts In the reparative stage, a stable collagen matrix network is established and temporary matrix proteins are removed punctually. Targeting the degradation of ECM and optimizing the secretion of ECM proteins will provide a complete skeleton support for cardiac regeneration, maintain the integrated heart structure and diastolic toughness, and then prevent heart function failure owing to abnormal ECM reconstruction.