Abstract: Mitochondrial Permeability Transition (MPT) is reported as the mechanism of acetaminophen induced hepatic damage, however, rat models are resistant to acetaminophen induced toxicity. The occurrence and degree of mitochondrial permeability transition after treatment with 400 mg kg–1 of acetaminophen in albino Wistar rats were assessed. Animals were randomly distributed into seven groups; control, 12, 24, 36, 48, 60 and 72 h based on varying time (in hour) post acetaminophen prior to sacrifice after treatment. Mitochondrial Membrane Permeability Transition (MMPT) pore opening and mitochondrial cytochrome c release were estimated. Opening of MMPT pore and cytochrome c release were observed in 12, 24, 36 and 72 h, when compared with the control group. Liver function and histological results indicated no liver damage. It is concluded that toxic dose of acetaminophen induced mitochondrial permeability transition in rat hepatic tissues without leading to necrotic damage suggesting that rat hepatic tissues evade damage by mechanisms downstream of MPT.