PLGA (Poli-lactic-co-glycolic acid) nanoparticles (NPs) are curently used as drug delivery systems for many types of drugs including antioxidants such as vitamin E. The main aim of our study was to test the antioxidant effects of PLGA-vitamin E on Wistar male rats. Two groups of Wistar rats received a hypercaloric diet for 21 days: the first group received besides the hypercaloric diet a daily dose of PLGA loaded with vitamin E and the control group received only the hypercaloric diet. Spleen cellular lysate has been used to detect biomarkers of oxidative stress such as malondialdehyde, glutathione, advanced human oxidative protein and vitamin E. After 3 weeks of treatment, statistical significant changes have been detected between the two groups.