Introduction: Dipeptidyl peptidase IV (DPP IV/CD26) is a multifunctional protein with a significant proteolytic and costimulatory role, thus affecting the process of proliferation, angiogenesis, adhesion, migration and apoptosis of cells in the wound healing process. It is also involved in the regulation of blood glucose concentrations by modulating the biological activity of incretins. However, the pathophysiological processes of wound healing in diabetes are not sufficiently clarified. The hypothesis of this study is that DPP IV/CD26 plays an important role in modulating the immune response in the wound healing process in conditions of hyperglycemia. The aim of this study was to determine whether DPP IV/CD26 deficiency affects macroscopic and/or microscopic changes during cutaneous wound healing process in diabetes. We aimed to determine the expression of macrophages and lymphocytes T in CD26 deficient and wild-type animals with induced diabetes and to investigate changes in serum DPP IV/CD26 activity during the development of experimental hyperglycemia and during the wound healing process in C57BL/6 animals. Materials and Methods: A model of diabetes was induced in CD26 deficient (CD26-/-) and wild type (C57BL/6) mice by intraperitoneal administration of a streptozotocin solution in citrate buffer at a dose of 50 mg/kg for five days. After the induction of diabetes, six experimental wounds (5 mm in diameter) were induced on the interscapular dorsal part of animals. Groups of experimental animals were sacrificed the second, fourth, seventh, tenth and fifteenth day of wound healing. Different methods of analysis were used for macroscopic and microscopic examinations (pathohistological, imunohistochemical, histomorphometrical and spectrophotometrical methods). The degree of regeneration of different skin layers, the degree of proliferation of the basal layer of epidermis and fibroblasts of the dermis, and the expression of lymphocytes T and macrophages in wound tissues of both mice strains were determined. Likewise, serum DPP IV/CD26 activity during the wound healing process in C57BL/6 mice was analyzed. The results of this study indicate a relatively more successful skin wound healing process under conditions of DPP IV/CD26 deficiency in diabetes. The rate of tissue regeneration in CD26-/- mice was statistically significantly higher (p<0.05) than in C57BL/6 mice as well as the number of Ki67 positive cells, indicating an increase drate of cell proliferation and regeneration of extracellular matrix in conditions of CD26 deficiency. The number of lymphocytes T is statistically significantly higher (p<0.05) in wild type mice indicating that the inflammatory phase is less pronounced in CD26-/-animals. The increase in macrophage expression was faster and more intense in the absence of DPP IV/CD26. The activity of serum DPP IV / CD26 in C57BL/6 diabetic mice was statistically significantly higher (p<0.05) compared to physiological conditions while it was significantly decreased the second and fourthday of wound healing. Conclusion: Obtained results confirm the hypothesis that DPP IV/CD26 influences the intensity and dynamics of wound healing as well as the specificity of the immune response in experimental hyperglycemic conditions. It has been shown that CD26-/-mice show a less pronounced inflammation response than wild type mice. The process of tissue regeneration and reparation in hyperglycemia is more successful in conditions of DPP IV/CD26 deficiency, which confirms the importance of inhibitors of this molecule for therapeutic purposes in patients with diabetes.