Chemoprevention of cancer is one of the reliable approaches to control the incidence of cancer. In the present study, we investigated the chemopreventive role of alpha-ketoglutarate (alpha-KG) during N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis. The activities of serum aspartate and alanine transaminases were found to be significantly higher in NDEA + CCl(4)-treated animals when compared with control animals. Administration of alpha-KG restored the activities of transaminases to near normal range. The levels of lipid peroxides, thiobarbituric acid reactive substances were decreased in the liver tissue of NDEA + CCl(4)-treated animals when compared with control animals. alpha-KG reversed the lipid peroxide levels to near normal range. Levels of antioxidants, reduced glutathione and activities of its dependent enzymes, glutathione peroxidase and glutathione-S-transferase were found to be significantly higher in liver tissue of NDEA + CCl(4)-treated animals when compared with control animals. alpha-KG administration positively modulated the antioxidant levels to near normal range. In conclusion, it can be suggested that alpha-KG exerts chemopreventive role which may attributable to its ability to positively modulate the transaminase activities and oxidant-antioxidant imbalance during hepatocarcinogenesis.