M2-like tumor-associated macrophages (M2-TAMs) in cancer tissues play a key role in cancer progression and immune evasion. Therefore, cancer immunotherapies targeting M2-TAMs have attracted considerable attention. Photodynamic therapy (PDT) is a minimally invasive and site-selective approach that kills target cells using a visible laser and a nontoxic photosensitizer. The photosensitizer is activated by the laser and produces reactive oxygen species (ROS) that induce cell death of target cells. We developed a novel photosensitizer, mannose-conjugated chlorin e6 (M-chlorin e6), which can be selectively delivered to M2-TAMs that highly express mannose receptors (CD206). We evaluated the anti-tumor effect of M-chlorin e6 PDT in a mouse model of allogeneic transplantation of CT26 cells, a murine colon cancer cell line. M-chlorin e6 PDT significantly reduced tumor volume and weight compared to the control group. M-chlorin e6 PDT also decreased the percentage of M2-TAMs (CD11b⁺, CD206⁺) and increased the percentage of M1-TAMs (CD11b⁺, CD80⁺ or CD86⁺, CD206^-) in the tumor tissue. Moreover, M-chlorin e6 PDT directly inhibited cancer cell viability and enhanced phagocytosis by the macrophage cell line RAW264.7. These results suggest that M-chlorin e6 PDT exerts its anti-tumor effect by reduction of M2-TAMs, inducing cancer cell death, and promoting macrophage phagocytosis.