Abstract: Trolox, an analogue of vitamin E, was firstly encapsulated into chitosan nanoparticles(20～40nm). In this way, the solubility of Trolox in water was increased about 27 times. Moreover, Trolox-chitosan nanoparticles showed better ability of protecting RAW264.7 cells from oxidative stress induced by t-BHP than Trolox alone at the same concentration. More importantly, the present study demonstrated a new strategy for elevating the solubility of antioxidants or drugs and improving their bioavailability by virtue of encapsulating them into nanoparticles.