The rectal insufflation of a judicious dose of ozone, selected from that used in clinical practice, is able to promote oxidative preconditioning or oxidative stress tolerance preventing the hepatocellular damage mediated by free radicals. In order to evaluate the effects of ozone oxidative preconditioning on carbon tetrachloride-mediated hepatotoxicity, the following experimental protocol was designed: group 1 (negative control, sunflower oil i.p.); group 2 (CCl 4 in sunflower oil, 1 ml kg -1 i.p.); group 3 (15 ozone-oxygen pretreatments at a dose of 1 mg kg -1 via rectal insufflation Y CCl 4 as in group 2); group 4 (ozone control group, 15 ozone-oxygen pretreatments Y sunflower oil i.p.). Ozone pretreatment prevented glycogen depletion (as demonstrated by biochemical and histopathological findings) and avoided lactate overproduction associated with the hepatotoxic effects of CCl 4 . The administration of CCl 4 increased lipid peroxidation (as measured by thiobarbituric acid-reactive substances) and uric acid levels and inhibited superoxide dismutase activity. All these deleterious effects induced by CCl 4 were prevented by ozone pretreatment. The administration of ozone without CCl 4 (ozone control group) did not produce any changes in the evaluated parameters. Our results showed that ozone treatment, in our experimental conditions, was able to prevent anaerobic glycolysis and oxidative stress induced by CCl 4 .