We evaluated the influence of the photodynamic therapy (PDT) dosage with hematoporphyrin monomethyl ether (HMME) on its therapeutic efficacy in a rabbit model of in situ rectal cancer. VX2 cells were injected into the rectal submucosa of a rabbit to establish a carcinoma model in situ. After 10-14days, the tumors were treated with PDT at three dosages: a low dose (5mg/kg HMME; 60J/cm(2) laser power), intermediate dose (5mg/kg; 240J/cm(2)), and high dose (10mg/kg; 360J/cm(2)). Tumor growth, animal survival, histopathological changes, general conditions, and adverse reactions were analyzed. PDT showed inhibitive effects on rectal cancer in all PDT groups, and the efficacy was correlated with the PDT dosage. The high dose PDT group had the best efficacy with a remarkable response rate of 20% and slight response rate of 80%, but it also had the highest death rate of 80% at day 7. The intermediate dose PDT group had a total response rate of 80% (60% remarkable plus 20% slight) and a 40% death rate. Comparably, the low dose PDT group had a 40% slight response rate and 60% death rate. Therefore, the intermediate dose of PDT was considered to be optimal among the three groups. Based on endoscopy findings, we also found that high dose PDT presented more side effects including inflammation, intestinal obstruction, rectal dysfunction, and death when PDT was performed on tumors inside the rectal tract. Our results indicate that a moderate PDT dose is more appropriate to treat tumors located in tract or cavity tissues.