Introduction. Ulcerative colitis (UC) is one of the two major pathohistological forms of inflammatory bowel disease. It represents an immune mediated disease which is characterized by recurrent episodes of the colon inflammation resulting in damage and loss of the intestinal mucosal function. It has been shown that the proteases dipeptidyl peptidase (DP)4 and recently discovered DP8 and 9 are involved in the modulation of immune mechanisms leading to colitis development as well as in the proliferation and activation of immune cells. Aim. Considering our previous results and experience, we hypothesized that changes in the expression of DP8 and 9 influence on the colitis development. Therefore, the aim of the research was to investigate the role of DP8 and 9, STAT3 and STAT6, and inducible nitric oxide synthase (iNOS) in the induction and progression of dextran sulfate sodium (DSS)-induced experimental colitis in mice. Material and Methods. Colitis was induced in C57BL/6 mice by oral administration of 3% solution of DSS. The health status of animals, changes in body weight, and development of clinical symptoms of colitis were monitored during the experimental period. Animals were sacrificed on day 7. Transcriptional expression of the DP8, DP9, STAT3, STAT6, and iNOS in the colonic tissue were evaluated by RT-qPCR. Results. The development of the colonic inflammation resulted in the appearance of clinical manifestations, an increase in the disease activity index, microscopic damage score and hepatosomatic index. A significant increase in transcriptional activity of DP8, DP9 in the colon was determined on the third day of the experimental period. Likewise, the increase in transcriptional activity of STAT3 and iNOS were determined on the day 3 and 7. Interestingly, development of the colon inflammation has not influenced on the STAT6 gene expression. Conclusion. The results indicate the importance of investigated proteases and signal molecules in the DSS colitis induction and progression.