The fundamental reason why the organic lesions of chronic heart failure are difficult to reverse is ventricular remodeling. Myocardial fibrosis (MF) is an important pathological basis of ventricular remodeling. Its development process involves complex biological mechanisms and neuroendocrine system. Extracellular signal-regulated kinase (ERK) pathway is a classic pathway for the treatment of tumors. It is found that the inhibition of the ERK pathway can also slow down the progressive aggravation of MF. Therefore, exploring the mechanism of ERK pathway in MF may provide a new idea for the prevention and treatment of chronic heart failure. In this paper, the mechanism of ERK pathway in the occurrence and development of MF and its inhibition drugs were described, in order to provide evidence for the prevention and treatment of MF in chronic heart failure based on this pathway.