To enhance the solubility and ocular permeability of immunosuppressive agent, cyclosporine A (CsA), three types of delivery systems were prepared using (2-hydroxypropyl)-β-cyclodextrin (HPβCD), and 2-hydroxyethyl methacrylate (HEMA). Those systems are (i) hydrogels of HPβCD with crosslinking agent ethylene glycol diglycidylether, (ii) poly(HEMA) hydrogels, and (iii) different amounts of HPβCD-containing poly(HEMA) hydrogels indicated as poly(HEMA-co-HPβCD). 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 HPβCD-based hydrogels by embedding from its aqueous suspensions in higher amounts than that of the poly(HEMA) hydrogels that were loaded by CsA–HPβCD complex solution. Although the poly(HEMA) hydrogels are releasing total CsA in 3 days, long-term release was realized from HPβCD-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-HPβCD) hydrogels in high HPβCD content. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40397.