Dietary coenzyme Q 10 prolongs lifespan of rats fed on a PUFAn-6-enriched diet.Our aim was to analyze changes in the levels of plasma proteins of rats fed on a PUFAn-6 plus coenzyme Q 10 -based diet. This approach could give novel insights into the mechanisms of lifespan extension by dietary coenzyme Q 10 in the rat. Serum albumin, which decreases with aging in the rat, was significantly increased by coenzyme Q 10 supplementation both at 6 and 24 months. After depletion of the most abundant proteins by affinity chromatography, levels of less abundant plasma proteins were also studied by using 2D-electrophoresis and MALDI-TOF mass fingerprinting analysis. Our results have shown that lifelong dietary supplementation with coenzyme Q 10 induced significant decreases of plasma hemopexin, apolipoprotein H and interalpha-inhibitor H4P heavy chain (at both 6 and 24 months), preprohaptoglobin, fibrinogen γ-chain precursor, and fetuin-like protein (at 6 months), and alpha-1-antitrypsin precursor and type II peroxiredoxin (at 24 months). On the other hand, coenzyme Q 10 -supplementation resulted in significant increases of serine protease inhibitor 3, vitamin D-binding protein (at 6 months), and Apo A-I (at 24 months). Our results support a beneficial role of dietary coenzyme Q 10 decreasing oxidative stress and cardiovascular risk, and modulating inflammation during aging.