Recent studies have disclosed that Mn-TPPS, a paramagnetic metalloporphyrin, may be a tumor-specific contrast media for magnetic resonance (MR) imaging. We investigated whether or not Mn-TPPS enhancement of the glioma could be mediated by peripheral benzodiazepine receptor. Using a transplanted rat C6 glioma model, Mn-TPPS enhancement was performed with or without pretreatment by peripheral or central benzodiazepine-specific receptor ligands. Signal intensity analysis disclosed that the enhancement was not inhibited by these ligands. Post-contrast replacement studies showed that neither of these ligands reduced Mn-TPPS enhancement. Although the tissue concentration of Mn-TPPS was significantly higher in the glioma than in the contralateral brain, PK11195 pretreatment did not replace the intratumoral Mn-TPPS. This data suggested that the tumor-specific enhancement of Mn-TPPS was not mediated by peripheral type benzodiazepine receptor.