Release of methylprednisolone from hyaluronic acid derivative corneal shields (Hyalobend), in vitro and in vivo, was evaluated as well as ocular anti-inflammatory activity in the rabbit eye. The release of methylprednisolone from Hyalobend corneal shields in vitro followed zero-order kinetics. After placing Hyalobend corneal shields in rabbit eye, aqueous and tear fluid methylprednisolone levels were detected up to 48 hours and compared with the levels obtained with methylprednisolone suspension. Hyalobend corneal shields maintained almost constant methylprednisolone levels in the rabbit tear fluid. On the contrary, the suspension gave very high tear values of steroid concentrations in the first 30 minutes but undetectable in less than 200 minutes. Hyalobend corneal shields ensured effective levels of methylprednisolone into the rabbit aqueous for up to 48 hours. Aqueous levels of drug, in the group treated with the suspension, decreased progressively and after 480 minutes were undetectable. Hyalobend corneal shields significantly reduced the conjunctival inflammation elicited by sodium arachidonate compared with control. Furthermore, Hyalobend corneal shields treatment significantly reduced the levels of PGE2 in the tear fluid. Hyalobend corneal shields increase the residence time of methylprednisolone in rabbit tear fluid and enhance the penetration into the aqueous humor as well as reduced the primary signs of ocular inflammation.