BACKGROUND: To explore the differences in tumor immune microenvironment between different KRAS mutation subtypes, and to provide a new direction for clinical immunotherapy of different subtypes of colorectal cancer. METHODS: We examined the spatial distribution of common inflammatory cell markers of CD8 + T cells, CD4 + T cells, natural killer cells, and B cells and macrophages in 55 colorectal cancer patients with different KRAS gene phenotypes using immunohistochemistry and panoramic scanning. We analyzed the relationship between inflammatory cells and clinical information. TCGA and String online databases were used to analyze the relationship between KRAS mutation subtypes and inflammatory cell markers. RESULTS: We observed that significant differences in the spatial distribution of the tumor invasion front and the immune cell infiltration within the tumor. Colorectal cancer patients with different KRAS mutations showed different immune infiltration, and the main cells with differences were FOXP3 regulatory T cells and M2 macrophages. Furthermore, these two cell types were strongly associated with the prognosis of KRAS wild-type and KRAS mutant colorectal cancer. CONCLUSIONS: The complexity of the immune microenvironment cannot be explained by infiltration of specific cell types alone, but may arise from cell-to-cell interactions or changes in the proportion of different immune cells. However, the infiltration of FOXP3 cells and M2 macrophages probably accounts for the differences between KRAS mutant subtypes.