Toxicity studies for intraperitoneal photodynamic therapy (IPPDT) were performed in Wag/RijA rats, using specially designed light delivery blocks for proper light distribution and light dosimetry. A recently developed photosensitizer mesotetrahydroxyphenylchlorin (mTHPC), excited at 652‐nm wavelength, was compared with Photofrin (630 nm). Toxicity profiles for various sensitizer doses, light fluences and time intervals were investigated. A light fluence of 15 J ‐ cm−2 delivered to the entire peritoneum 24 hr after 5 mg Photofrin per kg i.v. induced reversible impairment of intestinal, liver and kidney function. A dose of 0.2 mg mTHPC per kg i.v. followed by 6 J · cm−2 at 72 hr appeared to be equitoxic to the intestines; however, functional tests revealed little effect for this mTHPC‐mediated IPPDT regime on liver or kidney. Histology demonstrated focal irreversible damage to the kidneys for both photosensitizers, not reflected in functional impairment. Light doses of 25 to 30 J. cm−2 at 24 hr after Photofrin or 8–12 J · cm−2, 72 hr after mTHPC caused lethal toxicity in the first 2 weeks due to intestinal damage. Higher light doses caused a shock syndrome and rhabdomyolysis resulting in death within 20 hr for both photosensitizers. In conclusion, maximum tolerable schedules for whole‐abdomen IPPDT were defined for Photofrin and mTHPC. Both photosensitizers cause similar toxicity profiles depending on drug dose, light fluence and time interval.