Ulcerative colitis (UC) is a chronic inflammatory disease and its involvement area in colon is influenced by a complex network of gene interactions.We analyzed the weighted gene co-expression networks in microarray dataset from colonic mucosa of patients with UC and identified one gene co-expression module that was highly associated with the progression of involved area in UC colon (Pearson coefficient=0.81,P＜0.0001).In total,523 hub genes in this module were found to be involved in immune system process after enrichment analysis in Gene Ontology.By the STRING and Cytoscape analysis,we observed that interleukin-8 (IL-8) and matrix metalloproteinase-9 (MMP-9) were centered in the network of hub genes.We then detected the expression of IL-8 and MMP-9 in mucosa from left-sided colon of patients using quantitative PCR and immunofluorescence assay respectively.Both quantitative PCR and immunofluorescence assay revealed the expression levels of IL-8 and MMP-9 were significantly different among the healthy controls,left-sided colitis group and pancolitis group (P＜0.05).IL-8 and MMP-9 were detected with an enhanced expression in pancolitis as compared with left-sided colitis and healthy controls,respectively (P＜0.05).This study demonstrates that immune system process is indispensable in the progression of disease in colon,and identifies that IL-8 and MMP-9 play potential critical roles for the progression.