Abstract—Amoxicillin is realized as significant drug due to their essential inhibition of bacterial infections. However, the effective time of amoxicillin in clinical position is less than 8 hours. Therefore, this research was to prolong the drug delivery system. Chitosan was modified by PCL (PCL/CS) microparticles were fabricated by oil in water emulsion (o/w emulsion) techniques for the protection and controlled the release of amoxicillin. The ratio of PCL: chitosan at different ratios were investigated for their influences on the zeta potential, size, morphology, swelling ratio and the release rate of amoxicillin from PCL/CS microparticles. The encapsulation efficiency was 74% to 83% and the maximum cumulative released amounts of amoxicillin from the PCL/CS at ratio 1:5 was about 6.5±0.03 mg for 7 days. Furthermore, the antimicrobial of amoxicillin was demonstrated by antimicrobial activity assays, which are effective in treating Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The PCL/CS was enough for the bacterial inhibition growth of E. coli and S. aureus. The PCL/CS could be appropriate to supply a model the drug delivery system for the medical application.