This study was designed to investigate the potentially protective effects of Curcuma longa Linn. extract (CLE) on carbon tetrachloride (CCl 4 )-induced hepatotoxicity in rats. Male Sprague-Dawley rats were pretreated with 50 or 100 mg/kg of CLE or 100 mg/kg of butylated hydroxytoluene (BHT) for 14 days before CCl 4 administration. In addition, the CLE control group was pretreated with 100 mg/kg CLE for only 14 days. Three hours after the final treatment, a single dose of CCl 4 (20 mg/kg) was administrated intraperitoneally to each group. After the completion of this phase of the experiment, food and water were removed 12 h prior to the next step. The rats were then anesthetized by urethane and their blood and liver were collected. It was observed that the aspartate aminotransferase and alanine aminotransferase activities of the serum, and the hepatic malondialdehyde levels had significantly decreased in the CLE group when compared with the CCl 4 -treated group. The antioxidant activities, such as superoxide dismutase, catalase, and glutathione peroxidase activities, in addition to glutathione content, had increased considerably in the CLE group compared with the CCl 4 -treated group. Phase II detoxifying enzymes, such as glutathione S-transferase, were found to have significantly increased in the CLE group as opposed to the CCl 4 -treated group. The content of Nrf2 was determined by Western blot analysis. Pretreated CLE increased the level of nuclear translocated Nrf2, and the Nrf2 then increased the activity of the antioxidant and phase II detoxifying enzymes. These results indicate that CLE has protective effects against CCl 4 -induced hepatotoxicity in rats, via activities of antioxidant and phase II detoxifying enzymes, and through the activation of nuclear translocated Nrf2.Keywords: Curcuma longa Linn. extract, carbon tetrachloride, hepatotoxicity, antioxidant, phase II detoxifying enzyme, nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) -, H 2 O 2 , and · OH, which damage the liver [27,36]. These ROS are eliminated by antioxidants and phase II detoxifying enzymes such as glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST) [25,39]. Upregulation of many phase II detoxifying and antioxidant enzymes is mediated by antioxidant response elements (ARE). The transcription factor nuclear factorerythroid 2 (NF-E2)-related factor 2 (Nrf2) plays a pivotal role in the activation of ARE-driven antioxidant gene expression [6]. Nrf2 is a member of the "cap 'n' collar"