Objective: The role of macrophages in colorectal cancer tumorogenesis is complex because they can both prevent and promote tumor development. We investigated CD68 infiltration in tumor tissue and its correlations with proteins ot TGF-beta1 signaling pathway. Method: A nonselected panel of 206 primary tumors of colorectal origin was investigated immunohistochemically with antibodies against CD68, TGF-beta1, Smad4, Smad7, TGFRII and levels of TGF-beta1 were measured by ELISA. Results: Lower CD68 infiltration in tumor nests was associated with expression of TGF-beta1 (chi2 = 9.236, р = 0.002) and Smad4 (chi2=2.871, р=0.090) in tumor cells and with TGFRII expression (chi2=5.699, р=0.017) in tumor cells membranes. There was not correlation between CD68 cell numbers in tumor tissue and TGF-beta1 serum levels. We have found higher frequency of liver metastases in patients with lower infiltration with CD68 in invasive margin (chi2=11.364, р=0.001). The survival time was shorter for patients with low CD68 infiltration in tumor nests and invasive margin, compared with the survival time for patients, with higher CD68 infiltration in both tumor compartments (p<0.001). Conclusion: The increased levels of TGF-beta1 in the tumor have an immunosuppressive effect on CD68 infiltration.