Background <p>This study aimed to investigate the mechanism by which the Tet1/ARF-p53 pathway affects idiopathic pulmonary fibrosis (IPF) through macrophage polarization.</p> Methods <p>The polarization state of macrophages in IPF was analyzed, and the role of the Tet1/ARF-p53 pathway in macrophage polarization was examined. The expression changes of Tet1, ARF, and p53 were detected in both in vitro cell culture and in vivo animal models, as well as the levels of M1 and M2 macrophage markers.</p> Results <p>Tet1 regulated the DNA methylation status of the <i>ARF</i> gene, thereby affecting ARF expression and subsequently activating the p53 pathway. This regulation affected macrophage polarization, where M2 macrophage polarization was inhibited, ultimately alleviating the progression of pulmonary fibrosis.</p> Conclusion <p>The Tet1/ARF-p53 pathway plays a role in IPF by regulating macrophage polarization, providing a new potential therapeutic target for IPF.</p>