The basis of the difference in life expectancy between males and females is still unknown. Previous studies have provided compelling evidence for the presence of oxidized proteins, and lipids in advanced human atherosclerotic lesions. The gender factor responsible for such protein oxidation is unknown and controversial. Our aim was to reveal the difference between protein oxidation parameters of male and female rats of the same chronological age to understand the protein oxidation mechanisms enabling females live longer than males. In the current study, we investigated the relation between protein hydroperoxide levels (P-OOH) and other protein oxidation parameters such as protein carbonyl (PCO), total thiol (T-SH), advanced oxidation protein products (AOPP), and nitrotyrosine (NT). Our study also covered other oxidative stress parameters such as lipid hydroperoxides (L-OOH), and superoxide dismutase (SOD) activity in the plasma of male and female aged rats. Plasma P-OOH and AOPP levels of male rats were significantly higher compared with those of the female rats. T-SH levels were significantly lower in the aged male rats compared with those of the female rats. On the other hand, PCO, NT, and L-OOH levels, and SOD activity were all found to be not different. These data support the hypothesis that elevated levels of P-OOH and AOPP contribute to the extent of protein, but not lipid, oxidation in plasma of aged male rats. Furthermore, the results presented here may also rationalize studies, which have shown that protein oxidation is modulated on the basis of gender dependency. (c) 2007 Elsevier Ireland Ltd. All rights reserved.