OBJECTIVE Millingtonia hortensis Linn is an abundant resource of flavonoids, which might be beneficial in protecting liver tissue from injury. The hepatoprotective and antioxidant potential of ethanolic extract of M. hortensis on carbon tetrachloride (CCl(4)) induced hepatotoxicity and the possible mechanism involved therein were investigated in rats. METHODS Preliminary phytochemical studies were carried out to determine the total phenol and flavonoid contents. 30 adult Wistar rats were allocated into 5 groups. Control group received vehicle, group-2 received CCl(4) alone (1 ml/kg body weight, intraperitonially), groups 3 - 5 received the ethanolic flower extract in 2 dose levels (200 and 400 mg/kg) and Curcumin (100 mg/kg) as a standard for 8 days orally, followed by CCl(4) as a single dose on the 8(th) day. 48 hours later, blood was withdrawn, serum was subjected to biochemical assessments, and liver homogenate was examined for lipid peroxides, glutathione, superoxide dismutase, catalase and total protein levels. Furthermore, hepatic tissues were subjected to histopatological studies. RESULTS CCl(4) treatment produced a profound increase in the levels of malondialdehyde, hepatic marker enzymes and bilirubin content compared with the control (P < 0.05). Pre-treatment with the flower extract of M. hortensis significantly enhanced the levels of endogenous antioxidants and reduced the levels of hepatic marker enzymes in relation to the CCl(4) treated group (P < 0.05). Balloning degeneration and fatty changes in hepatocytes was prevented by pre-treatment with the flower extract. CONCLUSIONS The antioxidant nature of the flower extract of M. hortensis could be responsible for averting damage to the liver.