Photodynamic therapy (PDT) combines a drug or photosensitizer with a specific type of light to kill cancer cells. The cellular damage induced by PDT leads to activation of the DNA damage repair, which is an important factor for modulating tumor sensitivity to this treatment. beta-Glucans are natural polysaccharides that bind complement receptor 3 on the effector cells, thereby activating them to kill tumor cells during PDT. The hypothesis of the present study was that adjuvant therapy with beta-glucans would increase the efficacy of PDT. C57BL/6 female mice were subcutaneously implanted with Lewis lung carcinoma cells. Ten days after implantation, the mice were administered intravenously sodium porfimer (10 mg/kg) 24 h prior to laser irradiation, with or without oral administration of beta-glucan (400 microg/d/mouse, 5 days) from either barley, baker's yeast, or marine brown algae that contains the storage glucan, laminarin. Tumor volume and necrotic area in excised tumors were measured. The expression of proliferating cell nuclear antigen (PCNA) was determined as an indicator of the activity of the DNA damage repair system. PDT in combination with each beta-glucan significantly reduced tumor growth (P < 0.05, n = 10) and expression of PCNA (P < 0.001, n = 9), and increased necrosis in tumor tissues (P < 0.001, n = 9). Furthermore, each structurally different <beta-glucan exerted similar potentiating effects on PDT. The present findings show that beta-glucans enhance the tumor response to PDT, resulting in pronounced necrosis of PDT-treated tumors and suppression of the DNA damage repair system.