This study aims to investigate the effects of the trichloroacetic acid (TCA) on serum marker enzymes [aspartate aminotransferase (AST), alanin aminotransferase (ALT), creatine phosphokinase (CPK), acid phosphatase (ACP), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)], antioxidant defense systems [Reduced glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT)] and lipid peroxidation content (Malondialdehyde, MDA) in various tissues of rats. TCA (2000 ppm) as drinking water was administered orally to rats (Sprague-Dawley albino) ad libitum for 50 days continuously. TCA treatments caused different effects on the serum marker enzymes, antioxidant defense systems and the MDA content in experimented rats compared to controls. Results showed that TCA caused a significant increase in serum AST, ALT, CPK and ACP activity. The lipid peroxidation end product MDA slightly increased in the erythrocytes, liver and kidney of rats treated with TCA, whereas did not change in the brain. In addition, antioxidant enzyme activity such as CAT and SOD significantly increased in the brain, liver and kidney tissues of TCA induced group whereas the ancillary enzyme GR and the drug metabolizing enzyme GST activity did not significantly change in the all tissues. The observations presented led us to conclude that the administration of subchronic TCA promotes lipid peroxidation content, elevates tissue damage serum marker enzymes and fluctuates in the antioxidative systems in rats. Also the rats resisted to oxidative stress via antioxidant mechanism but the antioxidant mechanism could not prevent the increases in lipid peroxidation in rat's tissues. These data, along with the determined changes suggest that TCA produced substantial systemic organ toxicity in the erythrocyte, liver, brain and kidney during the period of a 50-day subchronic exposure. (C) 2007 Elsevier Inc. All rights reserved.