Impaired function of the central nervous system (CNS) in aged animals is associated with increased susceptibility to the development of many neurodegenerative diseases. Age-related functional deterioration in brain is consistent with the free radical theory of aging that predicts, among other things, that free radical reactions with and damage to biomolecules, such as proteins and membrane lipid bilayers, leads to loss of neurons and subsequently diminished cognition. These oxidatively modified biomolecules are believed to contribute to the decreased antioxidant content, mitochondrial dysfunction, and impaired plasticity in aged brains. Treatment of rodents with L-acetylcarnitine (LAC; gamma-trimethyl-beta-acetylbutyrobetaine) can improve these functional losses. Although it is well established that administration of LAC can decrease protein oxidation in aged brains, it is not clear which proteins are decreased in their level of oxidation in the brains of aged rats treated with LAC. The current study used a parallel redox proteomics approach to identify the proteins that are oxidized in aged rat cortex and hippocampus of aged rats. Moreover, those proteins that are reduced in oxidation status were identified in aged brains from rats treated in vivo with LAC. The findings are discussed in reference to brain aging and age-related cognitive impairment.