MicroRNAs (miRNAs) are gene expression's important posttranscriptional regulators. The precise function of miRNAs in ulcerative colitis (UC) is not entirely known. Our investigation's aim was to identify miRNAs induced in patients with active UC and to evaluate miR-141 influences on ameliorating intestinal inflammation. The miRNA expression profiles in patients suffering active UC (n = 15) and healthy individuals used as control (n = 13) were assessed adopting miRNA microarrays. Via quantitative real-time polymerase chain reaction, miR-141 expression was confirmed. Modulation of the objective gene CXCL5 expression through miR-141 was examined via luciferase reporter construct assays and miR-141 mimic or inhibitor transfections. The impacts of CXCL5 or miR-141 on AKT, MMP-2, and MMP-9 were examined via Western blot in HT29 cells. We found that in patients suffering active UC, miR-141 was substantially downregulated, and CXCL5 expression efficaciously increased. The results of luciferase reporter assays illustrated that miR-141 directly targeted CXCL5 and affected downstream expression of CXCL5 in HT29 cells. In addition, quiescent CXCL5 and the overexpression of miR-141 reduced levels of MMP-2 and MMP-9 in tumor necrosis factor-α-treated HT29 cells by means of repressing the inhibitory AKT. miR-141 seems to play a role in the bowel inflammation of individuals with active UC via downregulation of CXCL5 expression. This method may be related with the AKT activation signaling pathway.