Liver diseases are the major worldwide health problem about 50% of which is drug-induced rnhepatotoxicity. Cordia africana Lam. (Boraginaceae) is widely used in Ethiopian folk medicinernfor treatment of different types of liver disorders. The aim of this study was to investigaternhepatoprotective effects of aqueous (CAAE) and 80% methanol extracts of C. africana stem barkrn(CAME) and the solvent fractions of the CAME against acetaminophen (APAP)-induced liverrninjury in rats. APAP, 2 g/kg given orally, was used to induce liver injury. Blood samples wererntaken and serum levels of liver enzymes, and total bilirubin (TB) as well as lipid profiles wererndetermined. Histopathological examination of liver tissues was conducted to confirm thernfindings of biochemical analysis. Intra-peritoneal (I.P) sodium pentobarbital (SPB)-induced sleeprnduration was also used to determine the protective effect of the test substances. Oralrnadministration of APAP (2 g/kg) resulted in a significant increase in serum levels of alaninernaminotransferase (ALT) (227.80Â±40.80), aspartate aminotransferase (AST) (417.73Â±67.10),rnalkaline phosphatase (ALP) (248.33Â±34.55), TB (0.19Â±0.05), low-density lipoprotein (LDL)rn(13.03Â±1.70), total cholesterol (TC) (45.95Â±3.30) and triglycerides (TGs) (114.35Â±12.14) andrndecrease in serum high-density lipoprotein (HDL) (19.90Â±3.44). The levels of all thesernbiomarkers were reversed by the standard drug, silymarin 100 mg/kg. Administration of bothrncrude extracts at different doses and fractions also reversed serum levels of all the parametersrntested to ward normal. CAME exerted significant dose-dependent hepatoprotective effects inrnterms of ALT and AST, while the CAAE showed similar activity in terms of AST, ALP andrnTGs. The results of histopathological investigations confirmed the hepatoprotective effectsrnshown in the biochemical analysis. C. africana stem bark crude extracts and the solvent fractionsrnof the methanol extract showed hepatoprotective effects.