Mutations in the Wnt/β-catenin signaling pathway, which plays a crucial role in the development of normal human kidneys, can promote the development of renal fibrosis. Macrophages are closely associated with the development of interstitial fibrosis in transplanted kidneys. However, the role and mechanism of the Wnt/β-catenin signaling pathway in macrophages in transplanted renal interstitial fibrosis have not been elucidated. Here, we examined the expression of the Wnt/β-catenin signaling pathway in macrophages within chronic renal allograft dysfunction (CAD) patients’ allografts. Histological staining showed significant macrophage infiltration and cells coexpressing macrophage markers (CD68) and β-catenin composed a significant population in the interstitium of CAD allografts. Similarly, in the CAD model of C57BL/6J mice with a BALB/c renal allograft in which the renal allograft was infiltrated with a large number of macrophages expressing β-catenin. Macrophage-specific knockdown of β-catenin attenuated interstitial fibrosis and reduced the number of macrophages within the renal allografts. In addition, flow cytometry and immunohistochemical staining showed that macrophage-specific knockdown of β-catenin significantly reduced the proportion and number of both M1- and M2-type macrophages in a mouse CAD model. Mechanistically, pericyte-to-myofibroblast transformation (PMT) is one of the major contributors to renal fibrosis. Furthermore, PMT was found in the kidneys of both CAD patients and mouse CAD models. In the mouse CAD model, knockdown of macrophage β-catenin significantly attenuated PMT. In vitro, we constructed a co-culture model of bone marrow-derived macrophages (BMDMs) and pericytes. After ablating β-catenin in BMDMs, the M1-type BMDMs significantly attenuated PMT. This study suggests that activation of the Wnt/β-catenin signaling pathway in M1 macrophages promotes renal allograft interstitial fibrosis by inducing PMT.