Intravitreal injection of antibiotics has been shown to be effective in the treatment of bacterial endophthalmitis, but does not prevent the formation of fibrin. Recombinant tissue plasminogen activator (rTPA), a fibrinolytic agent, was evaluated in experimentally induced Staphylococcus aureus endophthalmitis in an animal model. Significant fibrinous reaction in the vitreous was present in three of six eyes treated with intravitreal injection of clindamycin and rTPA (50%) and in one of five eyes treated with clindamycin only (20%). Fibrin clot formation in the anterior chamber was present in two of six eyes treated with clindamycin and rTPA (33%) and not observed in the clindamycin treated eyes (0%). These findings suggest that rTPA does not play a beneficial role in the treatment of bacterial endophthalmitis in the presence of the vitreous.