Objective：To investigate the role and mechanism of iguratimod（IGT）in interstitial fibrosis of chronic renal allograft dysfunction（CAD）in transplanted kidneys. Methods：A mouse CAD model was constructed and validated. IGT was administered via gavage. Histological staining was used to assess injury and fibrosis in transplanted kidneys. Immunofluorescence staining，Western blot，and qRT - PCR were utilized to detect fibrosis markers and changes in macrophage - to - myofibroblast transition（MMT）in transplanted kidneys of the CAD mice. Transforming growth factor（TGF）-β was used to induce MMT in primary mouse bone marrow-derived macrophages（BMDM）in vitro，followed by IGT intervention. Transcriptome sequencing was employed to explore the downstream molecular mechanisms by which IGT regulated MMT. Results：The CAD groups developed severe interstitial fibrosis in the transplanted kidneys. Immunofluorescence staining revealed that markers related with MMT were significantly upregulated in the transplanted kidneys. Treatment with IGT markedly reduced interstitial fibrosis in the transplanted kidneys of the CAD mice at 16 weeks，along with a decrease in MMT cell numbers. In vitro experiments demonstrated that IGT significantly inhibited TGF-β-induced MMT，and cell transcriptome sequencing results suggest that IGT may mitigate MMT and reduced fibrosis by activating ferroptosis - related pathways. Conclusion：IGT may alleviate interstitial fibrosis in transplanted kidneys and slow the progression of CAD by upregulating the ferroptosis-related pathway to inhibit MMT. This may provide new insights for the future application of IGT in allograft kidney transplantation.