Abstract: Poly(styrenecoglycidyl methacrylate) (PSG) latex microspheres with epoxy groups on their surface are prepared by soapfree emulsion polymerization. PSG microspheres are surface grafted with 1, 6hexanediamine to prepare PSG1, 6hexanediamine(PSGN) microspheres. The pemetrexed disodium drug molecules are then covalently immobilized on the surface of the PSGN particles through the reaction with end amino groups. The factors of drug molecules covalent immobilization are studied. Results show that the pemetrexed disodium molecules covalent immobilization on the PSGN microsphere surface is mainly dependent upon the particle size and the concentration and distribution of active amino groups.