Tissue plasminogen activator(tPA) is a fibrin-specific fibrinolytic agent that has recently been shown to be effective in accelerating the clearance of hyphema. Intravitreal injection of tPA can promote rapid lysis of experimental intravitreal fibrin clots. The purpose of this study was to investigate the efficacy of intravitreal tPA injection for the treatment of vitreous hemorrhage in normal phakic non-vitrectomized rabbit eyes. Vitreous hemorrhages were produced by intravitreal injections of 0.05 ml of autologous whole blood in 25 rabbit eyes with intact vitreous. The injection of 25 or 100 micrograms of tPA in 15 eyes resulted in the clearance of vitreous hemorrhage in 99 ± 19 or 34 ± 6.5 days, respectively. This was significantly faster than in the control eyes in which the clearance was not seen until 131 ± 17 days later. No tractional retinal detachment was observed.