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This study aimed at evaluating the in vitro antioxidant and hepatoprotective activities of different stem bark extracts of Erythrina senegalensis prepared with ethanol, and the in vivo hepatoprotective activity and acute toxicity of the best extract. The 2, 4-diphenyl-1-picryl-hydrazil (DPPH) and microsomal lipid peroxidation (MLP) models, and the rat liver slices system were respectively used for the in vitro study. The Methylene chloride/methanol (1:1 v/v) (Emc) and 40% ethanolic (E40) extracts were more efficient in inhibiting MLP and in scavenging DPPH radical. However, E40 was most effective with regards to lactate dehydrogenase (LDH) leakage inhibition from rat liver slices intoxicated with carbon tetrachloride (CCl4). The in vivo hepatoprotective activity was evaluated against CCl4-induced hepatotoxicity in rats. The E40 extract (100 mg/Kg) significantly reduced the increase in ALT, AST and lipid peroxidation in liver homogenate, showing that the extract is as protective as silymarin at the same dose. Acute toxicity was evaluated in mice and E40 did not produce any behavioural changes or mortality even at an oral dose of 16 g/kg. The extract was found to contain antioxidant classes of compounds (flavonoids and polyphenols). In conclusion, the E40 extract of E. senegalensis could be an important source of hepatoprotective compounds.Key words: Erythrina senegalensis, stem bark extract, antioxidant, hepatoprotective, carbon tetrachloride.