Objective：This study systematically investigates the regulatory role and mechanism of interferon - gamma（IFN - γ）in Crohn’s disease（CD）-associated intestinal fibrosis. Methods：Intestinal fibroblasts were isolated from CD patients and treated with various cytokines[IFN-γ，interleukin（IL）-17A，IL-1β，IL-33，IL-36α，tumor necrosis factor（TNF）-α]in vitro. The mRNA expression level of amphiregulin（Areg）in human intestinal fibroblasts was detected using RT-PCR. Following treatment with 20 ng/mL IFN-γ for 48 h，transcriptome sequencing（RNA -seq）was performed，and a protein -protein interaction（PPI）network was constructed using the STRING database. Immunofluorescence was employed to detect myofibroblast markers such as alpha -smooth muscle actin（α-SMA） and antigen Kiel 67（Ki67），evaluating the effects of IFN-γ on the activation and proliferation of human intestinal fibroblasts. Results： Areg significantly promoted the activation，proliferation，and collagen synthesis of intestinal fibroblasts，whereas IFN - γ markedly suppressed Areg expression in intestinal fibroblasts and downregulated fibrosis - related genes including α - SMA，COL1A1，and COL6A1，while also inhibiting fibroblast proliferation and activation. RNA - seq analysis revealed that differentially expressed genes regulated by IFN-γ were significantly enriched in the extracellular matrix（ECM）remodeling pathway. PPI network analysis identified SRC as a core node，suggesting its potential role in mediating the anti -fibrotic effects of IFN -γ. Conclusion：Areg is a key mediator promoting intestinal fibrosis in CD. IFN-γ inhibits Areg expression through transcriptional regulation，and it is found that SRC may be a key effector molecule downstream of IFN-γ. IFN-γ may exert its anti-fibrotic effect by inhibiting the SRC/Areg signaling axis. These findings provide a theorectial basis for the development of anti-fibrotic strategies targeting the IFN-γ/SRC/Areg pathway.