〔Abstract〕 Objective To investigate the role of Vitamin D in the pathogenesis of inflammatory bowel disease(IBD) by studying the changes of inflammation related genes in peripheral blood mononuclear cells(PBMC). Methods 24 sample sizes were downloaded from GSE50012 in the GEO database, and they were divided into two groups: patients taking Vitamin D and patients not taking Vitamin D, with 12 patients in each group. Find out the differential expression of mRNA in PBMC of two groups of patients. At the same time, we conducted GO/KEGG and GSEA enrichment analysis on the differentially expressed genes, searched for possible pathways or molecular functions, conducted molecular interaction network analysis on the differential genes, and searched for key genes(Hub genes). A total of 128 patients with ulcerative colitis(UC) and 62 patients with Crohn′s disease(CD) in the outpatient department of our hospital were collected and divided into 4 groups by whether to take Vitamin D or not. Candidate key gene expression in PBMC in each group was measured to evaluate the effect of Vitamin D on inflammatory bowel disease. Results The GEO database screened a total of 128 differential expression genes(DEGs), of which 53 were highly expressed and 75 were low expressed. GO analysis showed that DEGs were mainly involved in cytokine activity, chemokine receptor binding, regulating inflammatory reactions, participating in immune response processes, mediating lymphocyte immunity, and other processes. KEGG analysis showed that cytokine receptor interaction, inflammatory bowel disease IgA mediated signaling pathways such as intestinal immune networks; GSEA analysis showed that the differentially expressed molecules were mainly involved in the Vitamin D receptor pathway and the KEGG chemokine signaling pathway. Protein interaction network analysis screened seven key genes, IL-6, MMP9, CXCL9, CXCL10, TREM1, IL1R2, and C1QB. After adding Vitamin D, HLA-DMA, HLA-DMB, IL-6, MMP9, CXCL9, and CXCL10 showed low expression, while NOD2 showed high expression. Conclusion Vitamin D may play a protective role in IBD by influencing PBMC inflammation related genes, thereby inhibiting inflammation and regulating immune function, providing ideas for the basic and clinical research of late IBD.