The present study reports the preparation and physicochemical characterization of surface-modified poly(lactide-co-glycolide) (PLGA) microparticles containing interleukin-2 (rhIL-2) for pulmonary delivery. The surface of the microparticles was modified with mucoadhesive polymers such as chitosan and Carbopol 971P. The feasibility of this surface modification was confirmed by measuring the zeta potential. Chitosan-modified PLGA microparticles showed a positive zeta potential, while Carbopol-modified PLGA microparticles were negatively charged. The mucin binding efficiency values have shown that the positively charged chitosan coated microparticles showed a higher adhesive percent to the mucin than the negatively charged un-coated or Carbopol 971P coated microparticles. Furthermore, surface modification of microparticles with chitosan and Carbopol 971P has yielded a slight decrease in the amount of protein initially released. These findings suggest the suitability of surface-modified PLGA microparticles as an efficient carrier system for delivery peptides and proteins to the respiratory tract.