ABSTRACT: Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD) characterized by occurrence in the rectum and sigmoid colon of young adults. However, the functional roles of transcription factors (TFs) and their regulating target genes and pathways are not fully known in ulcerative colitis (UC). In this study, we collected gene expression data to identify differentially expressed TFs (DETFs). We found that differentially expressed genes (DEGs) were significantly enriched in the target genes of HOXA2, IKZF1, KLF2, XBP1, EGR2, ETV7, BACH2, CBFA2T3, HLF, and NFE2. TFs including BACH2, CBFA2T3, EGR2, ETV7, NFE2, and XBP1, and their target genes were significantly enriched in signaling by interleukins. BACH2 target genes were enriched in estrogen receptor- (ESR-) mediated signaling and nongenomic estrogen signaling. Furthermore, to clarify the functional roles of immune cells on the UC pathogenesis, we estimated the immune cell proportions in all the samples. The accumulated effector CD8 and reduced proportion of naïve CD4 might be responsible for the adaptive immune response in UC. The accumulation of plasma in UC might be associated with increased gut permeability. In summary, we present a systematic study of the TFs by analyzing the DETFs, their regulating target genes and pathways, and immune cells. These findings might improve our understanding of the TFs in the pathogenesis of UC.