Myocardial fibrosis is the excessive deposition of extracellular matrix(ECM) in the cardiac interstitium caused by a variety of injury factors, which can lead to the decline of ventricular compliance, myocardial diastolic and systolic dysfunction and arrhythmia. It is closely related to the severity of cardiac insufficiency and poor prognosis. Fibroblasts, endothelial cells, pericytes and immune cells in cardiac interstitium can be divided into a variety of subgroups due to different genomic expression, and regulate myocardial fibrosis through phenotypic transformation, fine regulation of ECM components and secretion of pro-fibrosis or anti-fibrosis factors. This article reviews the role of cardiac interstitial cells in cardiac fibrosis and reveals the molecular mechanisms including signal transduction networks and epigenetic modifications, which will provide new therapeutic strategies and targets for preventing and alleviating cardiac fibrosis.