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The complex heterogeneity of intestinal mesenchymal cells makes it difficult to understand the pathogenesis of intestinal fibrosis. Previously, we identified Meflin as a marker of fibroblast subsets. This study aimed to explore the role of Meflin-positive fibroblasts in intestinal fibrogenesis and investigate the potential of pharmacological control of Meflin expression as a treatment for patients with CD. Our results indicated that Meflin expression was upregulated in fibroblasts at the early stage of fibrosis but was downregulated in established fibrosis in both patients with CD and 2 different mouse models, which are the chronic dextran sodium sulfate (DSS) model and an IL-10\u2013deficient model that spontaneously develops intestinal inflammation. Meflin-deficient mice exacerbated intestinal fibrosis with dysregulated expression of noncanonical Wnt ligand WNT5A and its receptor ROR2. 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