Objective：To elucidate the potential involvement of amphiregulin（AREG）in the pathogenesis of intestinal fibrosis in Crohn’s disease（CD）. Methods：Differentially expressed genes were identified through transcriptome sequencing following AREG （100 ng/mL）treatment of human intestinal fibroblasts for 48 h，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：RNA-seq analysis revealed that AREG enhanced the expression of lysophosphatidic acid receptor 3（LPAR3） in human intestinal fibroblasts. Clinical sample validation showed an increased LPAR3 expression at the fibrotic site，and plasma lysophosphatidic acid（LPA）levels were elevated in CD patients with intestinal fibrosis compared with those without. In vitro experiments demonstrated that AREG promoted the secretion of LPA by human intestinal fibroblasts，which subsequently increased the protein expression of LPAR3 and stimulated cell migration，proliferation，activation，and collagen production. The effects on cells were 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 may represent a promising therapeutic strategy for managing intestinal fibrosis.