A medium term bioassay of ethanolic extract of Vitex leucoxylon Linn (EVL) was evaluated for its anti-oxidant and anti-hepatocarcinogenic activity against Diethylnitrosamine (DEN) and Phenobarbital sodium (PB) against male Wister rats. The DEN given with single dose administration of 200mg/kg/i.p. and progression of cancer was promoted by PB at dose of 0.05% p.o./day in drinking water. After 6 weeks, on treatment with EVL at high dose showed significant increase in food intake, water intake, body weight and decrease in liver weight as that of 5- FU than low dose. Haematological parameters like Hb, Neutrophils, Monocyte, Lymphocyte, PCV showed significant increase with EVL at high dose but Total WBC and ESR showed significant decrease in EVL treated rats as that of 5- FU than low dose when compared to DEN+PB control. Serum biochemical parameters showed significant decrease in SGOT, SGPT, SALP, Urea, Creatinine, Bilirubin, Cholesterol, TGL and showed significant increase in Total protein, HDL in EVL treated rats as that of 5- FU than low dose when compared to DEN+PB control. Anti-oxidant study was performed in liver homogenate which showed decrease in LPO levels and increase in SOD, CAT, GPx, GR, GST, GSH in EVL treated rats as that of 5- FU than low dose when compared to DEN+PB control. Histopathological studies of rat liver in EVL treated liver showed protective effects in higher dose treated group with no much loss in cell architecture as that of standard than the lower dose treated group when compared to DEN+PB control rats. Hence it can be concluded that ethanolic extract of Vitex leucoxylon Linn possesses significant anti-hepatocacinogenic activity in rats.