Permanent polysaccharide coating on gigaporous polystyrene (PS) microspheres was achieved through direct chemical grafting of dextran via a facile method, minimizing nonspecific adsorption of proteins and providing easily derivatizable groups on microspheres. Chloroacetylated PS microspheres (PS-Cl) were first developed through acetylation, and hydrophilic dextran was directly grafted to hydrophobic PS-Cl via a Williamson reaction (PS-Dex). The homogeneous side-bound dextran coating has the advantage of masking the hydrophobic surface of the PS microspheres, while maintains their original gigaporous structure. After grafting, the hydrophobic surface of the PS microspheres was effectively masked, and nonspecific protein adsorption was greatly reduced. Moreover, the hydroxyl-rich coating can be easily derivatized through classical chemical methods. A column packed with PS-Dex presented both good permeability and mechanical strength at high flow velocities of up to 3612 cm/h. These results implied that PS-Dex should be an ideal matrix for highspeed protein chromatography. (C) 2016 Society of Plastics Engineers.