The objective of this study was to evaluate the effect of a single photodynamic therapy (PDT) on brain edema and intracranial pressure (ICP) in a rabbit model of brain tumor. A total of 57 adult New Zealand rabbits were assigned to 3 groups: the PDT group, the tumor group, and the tumor plus PDT group. Rabbits in the PDT group (n = 9) received PDT but no tumor implantation; rabbits in the tumor group (n = 18) received VX2 carcinoma implantation but no PDT; rabbits in the tumor plus PDT group (n = 30) received tumor implantation with subsequent PDT 16 days later. Brain edema and ICP levels were then evaluated. We found that ICP in the PDT group was 7.43 +/- 0.50 mmHg. After tumor implantation, ICP increased rapidly (18.43 +/- 1.10 mmHg, 21 days later). PDT alone did not increase ICP, but compared with that in the tumor group, ICP increased significantly in the tumor plus PDT group (9.55 +/- 1.32 vs. 13.31 +/- 1.13 mmHg, p < 0.01) 24 hours after treatment. Brain water content in the tumor group increased rapidly after tumor implantation. PDT again increased perineoplastic brain edema 24 hours after treatment (81.09 +/- 0.97% vs. 78.32 +/- 0.49%, p < 0.01). It should be noted that PDT alone did not induce brain edema. In conclusion, PDT causes transient brain edema and increases ICP in a rabbit brain tumor model.