AIM: To investigate the anti-tumor effects of combined cytotoxic drug (gemcitabine) and photodynamic therapy (PDT) on human pancreatic cancer xenograft in nude mice. METHODS: Human pancreatic cancer cell line SW1990 was used in the investigation of the in vivo effect of combined gemcitabine and PDT on human pancreatic cancer xenograft in mice. Sixty mice were randomly allocated into a control group (without treatment), photosensitizer treatment group (2 mg/kg photosan, without illumination), chemotherapy group (50 mg/kg gemcitabine I.p.), PDT group (2 mg/kg photosan + laser irradiation) and combined treatment group (photosan + chemotherapy), with 12 mice in each group. Tumor size was measured twice every week. Anti-tumor activity in different groups was evaluated by tumor growth inhibition (TGI). RESULTS: No significant anti-tumor effect was observed either in photosensitizer treatment group or in chemotherapy group. PDT led to necrosis in cancer lesions and significantly reduced tumor volume compared with photosensitizer on day 6 and at the following time points after initialization of therapy 0.09, P < 0.05). PDT significantly reduced tumor volume in combined treatment group compared with P < 0.05). TGI was higher in the combined treatment group (82.42%) than in the PDT group (58.18%). CONCLUSION: PDT has a significant anti-tumor effect, which is maintained for a short time and can be significantly enhanced by small doses of gemcitabine.