Dipeptidyl-peptidase IV (DPP IV/ CD26) is a transmembrane glycoprotein involved in the modulation of immune response through its proteolytic, costimulatory and signaling function. Previous studies have shown decreased DPP IV/CD26 activity in patients with inflammatory bowel disease (IBD). IBD are immune-mediated chronic disorders of complex etiology. Depending on the localization and symptoms two clinical, pathomorphological forms are present, ulcerative colitis (UC) and Crohn's disease. Recent data suggest that the course of development of UC, nature and intensity of the inflammatory response, depends on the profile of inflammatory cells and mediators. In order to expand knowledge about the role of DPP IV/CD26 in modulation of the immune response, the aim of this study was to examine the impact of DPP IV/CD26 deficiency on the activation of macrophages and the expression of chemokines, monocyte chemotactic protein (MCP) -1 and macrophage inflammatory protein (MIP) -1 in vivo model of colitis. The experimental model of colitis was induced in wild type (C57BL/6) and DPP IV/CD26 deficient mice (CD26-/-) using sodium dextran sulfate solution. The establishment, development and resolution of colitis were monitored on the basis of clinical and histopathological parameters. Characterization of cells in intestinal mucosa was determined by immunohistochemistry and the expression of genes by polymerase chain reaction. Development of colitis was followed by a significant decline in body weight, change of the length of the colon and increase in spleen weight and disease activity index in both groups of mice. Significant loss of body mass and disease activity index were observed in CD26-/- was more intensive than in C57BL/6 mice, in spite of similar histopathological changes at the local level. During recovery, CD26-/- mice restore body mass faster than C57BL/6 mice. In the acute phase increase in the number of macrophage was present in both mouse strains. In CD26-/- the increase was twice than in C57BL/6 animals. The development of colitis was accompanied with a significant increase in the expression of MCP-1 and MIP-1 in both mouse strains but the increase in the acute phase of colitis was significantly higher in CD26-/- mice. This research offers a new insight into the role of DPP IV/ CD26 in activation of macrophages and thereby modulating the immune response during the development of colitis.