To enhance the solubility and ocular permeability of immunosuppressive agent, cyclosporine A (CsA), three types of delivery systems were prepared using (2-hydroxypropyl)--cyclodextrin (HPCD), and 2-hydroxyethyl methacrylate (HEMA). Those systems are (i) hydrogels of HPCD with crosslinking agent ethylene glycol diglycidylether, (ii) poly(HEMA) hydrogels, and (iii) different amounts of HPCD-containing poly(HEMA) hydrogels indicated as poly(HEMA-co-HPCD). In the presence of HEMA, hydrogels have desired mechanical integrity with lower equilibrium content than that of hydrogels without HEMA. CsA was loaded into the HPCD-based hydrogels by embedding from its aqueous suspensions in higher amounts than that of the poly(HEMA) hydrogels that were loaded by CsA-HPCD complex solution. Although the poly(HEMA) hydrogels are releasing total CsA in 3 days, long-term release was realized from HPCD-based hydrogels. For subconjunctival administration, regarding to the amounts of loaded CsA, release profiles, and mechanical integrity, the most suitable system is poly(HEMA-co-HPCD) hydrogels in high HPCD content. (c) 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40397.