Uterine carcinosarcoma is an aggressive neoplasm with low survival rates because of the lack of very effective chemotherapy protocol. Photodynamic therapy (PDT) is recently suggested to be an efficient protocol for this cancer. Pheophorbide a (Pa) is a chlorophyll degradation product in the green plant cells, its antitumor effect was reported on a number of human cancer cells with PDT approach. This study demonstrated that using Pa in PDT (Pa-PDT) significantly inhibited the human uterine sarcoma cell line MES-SA with an IC50 value of 0.5 μM at 24 h. Induction of apoptosis was found on the Pa-PDT treated cells according to the results of propidium iodide (PI) staining, annexin-V staining and DNA fragmentation assay. Pa was found to be localized in the mitochondria that lead to the depolarization of mitochondrial membrane potential by the rapid generation of singlet oxygen during light irradiation, where release of cytochrome c was detected and lead to the activation of intrinsic apoptotic pathway in MES-SA cells. Our findings revealed the therapeutic potential of Pa-PDT on the human uterine cancer.