Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by epithelial-mesenchymal transition (EMT) as a key feature. The study investigated the role of ESRP1 protein in the regulation of EMT using bleomycin-induced IPF mouse models. Single-cell RNA sequencing (scRNA-seq) showed significant increased expression of ESRP1 in alveolar epithelial cells versus controls. Knockdown of ESRP1 suppressed the expression of Epac, Rap1a and N-cad in epithelial cells, while its overexpression enhanced them. Co-IP confirmed the interaction between ESRP1, Epac and Rap1a, whereas silencing Epac or Rap1a did not alter ESRP1 expression. These findings demonstrate that increased ESRP1 expression in alveolar epithelial cells promotes IPF progression through activation of the EPAC-RAP1A axis in EMT.