Caloric restriction (CR) decreases aging rate and lowers the rate of reactive oxygen species (ROS) production at mitochondria in different organs, but the signal responsible for this last change is unknown. Glucocorticoids could constitute such a signal since it is well known that their levels increase during CR, and available studies failed to find consistent effects of insulin, the other better described hormone that varies during CR, on mitochondrial oxidative stress. In addition, there is almost no information on the possible in vivo effects of glucocorticoids on specific markers of mitochondrial and tissue oxidative stress. In this investigation, male Wistar rats were treated with corticosterone at doses of 150 and 400 mg/kg of diet during 4 weeks. After that time, oxidative stress-related parameters were measured in the liver. The corticosterone treatments did not change the rate of ROS production or the rate of oxygen consumption of rat liver mitochondria. The two lipoxidation protein markers measured (malondialdehyde-lysine and carboxymethyllysine) were decreased by both corticosterone treatments. These changes were associated with decreases in fatty acid unsaturation, especially with lowered levels of the highly unsaturated araquidonic and docosahexaenoic acids, which decrease the sensitivity to lipid peroxidation processes. The specific protein carbonyl glutamic semialdehyde, a marker of protein oxidation, was also lowered at 400 mg/kg corticosterone. The protein glycoxydation marker carboxyethyllysine and the level of oxidative damage to mtDNA (8-oxo-7,8-dihydro-2 9-deoxyguanosine) were increased by corticosterone. The results do not support the idea that corticosterone is the signal responsible for the decrease in mitochondrial ROS generation during CR. However, they show that this hormone modulates the level of oxidative stress both in proteins and in mtDNA. Some of these changes can contribute to the chronic effects of the hormone at tissue level.