The most reliable and robust risk factor for some neurodegenerative diseases is aging. It has been proposed that processes of aging are associated with the generation of reactive oxygen species and a disturbance of glutathione homeostasis in the brain. Yet, aged animals have rarely been used to model the diseases that are considered to be age-related such as Parkinson's or Alzheimer's disease. This suggests that the results from these studies would be more valuable if aged animals were used. The present study was designed to provide insight into the glutathione redox state in young and aged rat siblings of both genders by studying the enzyme activities related to glutathione synthesis, cycling, and usage. The results suggested a significant age-related reduction of reduced glutathione (GSH) level in all brain regions examined, associated with an increase of GSH oxidation to glutathione disulfide (GSSG) and decrease of the GSH/GSSG ratio. These changes were accompanied by diminished gamma-glutamylcysteine synthetase activity in de novo glutathione synthesis and increased lipid peroxidation. In addition, these changes were associated with increased enzyme activities related to the GSH usage (glutathione peroxidase, gamma-glutamyl transpeptidase, and glutathione S-transferase). The results indicate that aged animals are likely more vulnerable to oxidative stress and insinuate the roles of aged animals in modeling age-related neurodegeneration diseases.