Intraocular fibrin formation following ocular surgery is a potentially binding problem. Current therapy for this postoperative fibrin response is often ineffective. In the rabbit, we developed a quantitative reproducible model for intraocular fibrin deposition. Using this model, we have tested the efficacy of human tissue plasminogen activator (tPA) in promoting intraocular fibrinolysis. Citrated rabbit plasma (0.2 mL) was injected intracamerally following paracentesis, resulting in fibrin clot formation within three hours. The fibrin clots were stable for four days, and then slowly lysed over the next four days. Approximately 24 hours after clot formation, various concentrations of human tPA were injected intracamerally. The time taken for clot lysis was dose dependent, with 1800 IU of tPA producing clot lysis in three hours. Toxicity, as measured by intraocular pressure, corneal thickness, inflammation, or cataract formation, was minimal.