Immunofluorescence assays revealed that RCEO effectively downregulated the expression of Tlr4 and Pi3k in macrophages, thereby exerting a protective effect against pulmonary fibrosis.<h4>Conclusion</h4>RCEO ameliorates PF by suppressing both M1 and M2 polarization of macrophages via inhibition of the Pi3k/Akt/β-catenin and Tlr4/Myd88/Nf-κb signaling pathways. Here, MYD88 is linked to pemphigus foliaceus.