The vaginal retention and local irritation of a carrageenan, poloxamer 407 and carbopol-based thermosensitive hydrogel system for vaginal drug delivery was assessed. Results showed that the residence of hydrogel in the mouse vagina following intravaginal administration was prolonged by carrageenan and further prolonged by the addition of a mucoadhesive component (carbopol). The optimal hydrogel formulation was proven to be safe for vaginal use in rabbits.