Abstract: In this study, ceftriaxone-loaded microspheres were prepared by an inverse emulsion polymerization method using starch as raw material. The effects of cross linking agent, glutaraldehyde and the time of cross linking on antimicrobial behavior of drug loaded-microspheres were investigated against Salmonella typhi, Salmonella paratyphi A and Salmonella paratyphi B. Surface morphological characteristics and size distribution of prepared microspheres were studied by using an optical microscope. Microspheres loaded by ceftriaxone displayed different activities against microorganisms. The maximum diameter of inhibition zone caused by the microspheres was 19 mm and prolonged release pattern for 24 h. Microspheres had spherical shape and the size of cross linked microspheres was larger than uncross linked ones. Their size distributions were between 1 to 40 μm. It is probable, with more study, to increase the efficacy of treatment by this method.