Objectives: Colorectal cancer is the second leading cause of mortality in the group of malignant diseases in developed countries. The etiopathogenesis of this disease is stress, genetic and environmental factors, chronic inflammation, nutrition, age, habits, viruses, suffered cancer. Cells of innate and acquired immunity using different mechanisms of killing tumor cells and interrogation changes the immune status, as well as the number and function of specific subtypes of lymphatic cells, importance in the diagnosis and prognosis of these patients, opening up various possibilities for further development of immunotherapy. NKT cells are a subset of T cells that share properties of natural killer cells and conventional T cells. They are involved in innate immune responses, tumor rejection, post transplantation immunotherapy, immune surveillance and control of autoimmune diseases, as well as, in a number of pathological conditions, and have been shown to regulate viral infections in vivo, and control tumor growth. They may also play both protective and harmful roles in the progression of certain autoimmune diseases, such as diabetes, lupus, atherosclerosis, and allergen-induced asthma. NK cells and cytotoxic T lymphocytes can use the perforin/granzyme pathway to kill virally infected cells, as well as tumor cells. Dysregulation of this pathway can be associated with the appearance of many serious diseases VI Patients and Methods:.The aim of this study was to investigate the characteristics of human regulatory T and NKT cell, using a flow cytometric technique (FACSCalibur) for detecting phenotype of isolating human peripheral blood lymphocytes (PBL), as well as the lymphocytes from the irrigating areas of lower mesenteric vein, of patients with colorectal carcinoma on systemic and local levels, comparing to healthy volunteers. Simultaneously, with the phenotype of lymphatic cells determined by FACS staining, the spontaneous cytotoxic activity of freshly isolated MNLC was measured against NK-sensitive target. Statistical analysis was done in computer program Statistica 7.1 (StatSoft, Inc., Tulsa, OK, USA). Graphs and tables were done in computer program Microsoft Excel. Results: Our results showed that the total perforin, as well as the percentage of double-positive (perforin +, surface antigen + cells) significantly decreased at the local and systemic level, while the percentage of NKT and Treg cells markedly increased, especially at the local level. Cytotoxic activity of mononuclear cells of patients with colorectal cancer was significantly reduced compared to control. Conclusion: Our results indicate that decreased expression of the cytolytic molecule perforin in mononuclear cells of patients with colorectal cancer at the local and systemic level, gaining an important role of perforin in the immune response. Immunoregulation role of innate immunity cells (NKT and regulatory T cells) is great especially at the local level, and may provide impetus to the development of new strategies