The study was set to investigate the potency of stem bark extract of Sterculia setigera as a hepatoprotective agent against acute administration (overdose) of acetaminophen in experimental animals. Experimental animals were grouped into six treatments with each group containing five rats. Group 1 was the placebo, Group II was the standard treatment orally administered acetaminophen at a dosage of 250 mg/kgbw and thereafter treated with the standard drug silymarin at 100 g/kgbw after 6 h, to Group III (negative treatment) was orally administered acetaminophen only, at a dosage of 250 mg/kgbw without follow up treatment with standard drug (silymarin). Groups IV, V and VI were orally administered 70% methanol stem bark extract at a dosage of 200, 400 and 600 mg/Kgbw six hours after being orally administered with the hepatotoxic acetaminophen. The trial treatment was carried out for a period of three weeks. The inadequacy of herbs used in curing of liver diseases and other dysfunctions caused by allopathic drugs is enough reason to focus on systematic scientific research to evaluate some species of plants that are traditionally claimed to possess hepato-protective activities.