In conclusion, we demonstrated the important role of EZH2 in mediating the progression from AKI to CKD by promoting EMT via binding to the PTEN promoter and regulating its transcription, thus promoting the activation of EGFR/ERK1/2/STAT3 signaling pathway, and activating the polarization of M2 macrophages via STAT6 and PI3K/AKT pathway, eventually led to kidney fibrosis. Here, EZH2 is linked to chronic kidney disease.