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Plants and their components are the only source of most drugs which comprise of distinct groups such as antispasmodics, emetics, anticancer and antimicrobials. Plants capable of improving health conditions and treating diseases have been identified and used since human existence. A wide variety of compound synthesized from plants participate in biological roles such as defense against predators. This study examined the protective effect of Aframomunchrysanthum seed aqueous extract against acetaminophen-induced liver toxicity in rats. A suspension of 750 mg/kg acetaminophen was administered once every 72 hours to induce toxicity in the rats. This was followed by oral administration of the plant extract (500, 1000 and 2000 mg/kg) body weight and 100 mg/kg of silymarine. For ten days. Eighteen hours after the last dosage, blood sample was collected for biochemical analysis. The result showed significant (p < 0.05) increase in the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) as well as the concentrations of albumin (ALB) and total bilirubin (T. B) levels in rats administered with acetaminophen only. The levels of these parameters were significantly (p < 0.05) decreased in the groups pretreated with the extract.