This study investigated the acute toxicity effect of aqueous stem bark extract of Lophira lanceolata and the activities of liver enzymes and other markers of organ damage in rats pretreated with aqueous stem bark extract of L. lanceolata extract and subsequently intoxicated with paracetamol (PCM). A total of 30 rats were used to determine the acute toxicity of aqueous extract of L. lanceolata stem. They were divided into six groups consisting of five rats each. The groups (A-F) were administered the increasing doses of the extract (500 mg/kg, 1,000 mg/kg, 2,000 mg/kg, 3,200 mg/kg, 4,000 mg/kg and 5,000 mg/kg) orally. The rats were observed over a period of 24 h for acute toxicity signs such as dullness, anorexia, morbidity and death. Thirty rats of mixed sexes randomly assigned to six groups (A-F) of five rats each were used for the study on the effects of L. lanceolata extract on the haematology, liver enzymes and markers of organ damage of extract-pretreated PCM-intoxicated rats. The rats in groups A-D were pretreated with 100 mg/kg, 200 mg/kg, 300 mg/kg of L. lanceolata extract and 100 mg/kg Silymarin, respectively, twice a day for 7 days. On the seventh day, all the rats in groups A-E received 1,000 mg/kg PCM (per os). Group E rats served as negative control while group F rats were neither intoxicated nor treated with the extract and served as positive control. Eighteen hours after PCM intoxication, blood samples were collected for biochemical analyses. The serum activities of these enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP]) and other markers of organ damages (bilirubin and total protein) were investigated. Haematologic parameters such as packed cell volume, red blood cell count, white blood cell count and haemoglobin concentration were also determined. The extract did not cause any death in all the groups even at the highest dose (5,000 mg/kg body weight). The results also showed varying degrees in the activity of the enzymes in the serum in comparison with the negative control. The mean serum ALP, ALT and AST activity of group C (rats pretreated with 300 mg/kg of the extract and 1,000 mg/kg PCM) were significantly (p<0.05) lower than that of the group E (rats intoxicated with 1,000 mg/kg PCM only). The AST and ALP activities of groups C-E rats) were statistically comparable. The serum ALT activities of group C rats were significantly (p<0.05) lower than that of group E rats but were statistically comparable (p>0.05) with the group F counterpart. The bilirubin levels were significantly (p<0.05) lower in the groups pretreated with the extract and Silymarin in comparison with the D group. The total protein and the haematologic indices were not significantly different (p>0.05) across the groups. This study therefore showed that the aqueous stem bark extract of L. lanceolata possesses some active constituents that have antihepatotoxic potentials.