Indigofera linnaei Ali., has been widely used in folk medicine to treat inflammation, liver disorders and swelling of stomach. Earlier studies showed that methanolic extract of Indigofera linnaei (MEIL) possess antioxidant, free radical scavenging, antitumour, anti-inflammatory and analgesic activities but its effect on chemoprevention on chemical induced carcinogenesis have not been studied. Hence the present study is aimed to investigate chemopreventive efficacy of MEIL against diethylnitrosamine (DEN) induced phenobarbital promoted rat liver carcinoma model. Liver tumour was induced in rats by intraperitoneal administration of DEN (200 mg/kg). After two weeks, the carcinogenic effect was promoted by phenobarbital given through drinking water for 16 successive weeks. MEIL (200 and 400 mg/kg/day) and silymarin (200 mg/kg/day) were administered orally for entire study period. After the experimental period, changes in body weight, liver weight, relative liver weight, tumour incidence, antioxidant, serum hepatic parameters, serum specific tumour markers, nucleic acid and protein content were analysed. MEIL treatment significantly increased the body weight, reduced the liver weight and tumour incidence, restored the altered serum hepatic parameters, down-regulated the serum tumour markers such as alpha fetoprotein, carcinoembryonic antigen, vasculoendothelial growth factor and tumor necrosis factor-a. In addition, treatment with MEIL restored the antioxidant enzyme pool and significantly reduced the lipid peroxidation in carcinogen treated animals. MEIL treatment also reduced the elevated levels of nucleic acid levels and restored the protein content in liver tissues. The results suggested that MEIL would be a potent chemopreventive agent inhibiting chemically induced hepatic cancer.