Abstract Myocardial fibrosis (MF) is involved in hypertension, myocardial infarction and heart failure. It has been reported that circular RNA (circRNA) is a key regulatory factor of MF progression. In this study, we revealed that circ_0002295 and CXCR2 were elevated, and miR‐1287 was reduced in MF patients. Knockdown of circ_0002295 effectively suppressed the proliferation, migration and MF progression. Circ_0002295 was the molecular sponge of miR‐12878, and miR‐1287 inhibitor reversed the biological functions of circ_0002295 on the myocardial fibrosis. CXCR2 was a target gene of miR‐1287, and CXCR2 silencing relieved the impacts of miR‐1287 inhibitor on cardiac myofibroblasts. Circ_0002295 promoted MF progression by regulating the miR‐1287/CXCR2 axis, providing a possible circRNA‐targeted therapy for MF.