We had previously reported that transferring of M2 macrophages to the recipient’s lung could reduce the expression of TGF-β1 in the recipient’s lung [5], in this current study, we identified EZH2 inhibitor could modulate M2-like macrophage polarization in the BALF of ARDS mice, and further interact with epithelial cells and inhibit the EMT through the regulation of TGF-β1/Smad signaling pathway. This evidence concerns the gene EZH2 and acute respiratory distress syndrome.