To elucidate the potential involvement of amphiregulin (AREG) in the pathogenesis of intestinal fibrosis in Cronh’s disease(CD). Methods: Differentially expressed genes were identified through transcriptome sequencing following AREG(100ng/ml) treatment of human intestinal fibroblasts for 48h, aiming to uncover the underlying mechanisms by which AREG contributes to intestinal fibrosis; Fibrotic and non-fibrotic tissues were obtained from CD patients undergoing surgical resection for clinical validation; cell proliferation and migratory capacity were assessed via Ki67 immunofluorescence and scratch assays, while expression levels of Col1a1、Col6a1、and Col6a3 were quantified using qRT-PCR and α-smooth muscle actin(α-SMA) was quantified by Western blot. Results: Analysis of RNA-seq data revealed that AREG enhances the expression of lysophosphatidic acid receptor 3(LPAR3) in human intestinal fibroblasts. Additionally, elevated levels of lysophosphatidic acid (LPA) were found in the plasma of CD patients with intestinal fibrosis compared to those without it, while LPAR3 expressions increased at the sites affected by fibrosis as opposed to nonfibrotic sites from CD patients. In vitro experiments demonstrated that AREG promotes the secretion of LPA by human intestinal fibroblasts, which subsequently increases the protein expression of LPAR3 and stimulates cell migration, proliferation, activation, and collagen production. The effects on cells can be attenuated by LPAR3 inhibitors. Conclusion: AREG may play a significant role in the pathogenesis of CD-related intestinal fibrosis through the LPA-LPAR3 signaling pathway; thus, targeting the AREG-LPA-LPAR3 axis could represent a promising therapeutic strategy for managing intestinal fibrosis.