Objective: To report the effectiveness of recombinant human tissue plasminogen activator (rtPA) in severe post-operative fibrinous reaction. Method: The presentation of a case series. Result: Four patients developed severe post-operative inflammation about six days after an otherwise uneventful cataract surgery. Three women, with an average age of 63.25 years old, were included. At the same time, three patients had underlying comorbidities such as diabetes mellitus and hypertension. The average duration of the operation was 31.25 minutes. All operations were performed by different surgeons. All underwent uneventful cataract surgery. They presented with a dense fibrin in anterior chamber within a week of post-operative review. All patients received 25 micrograms in 0.1 mL of intracameral rtPA injection. Assessment included anterior chamber fibrin reaction before and after injection by slit lamp biomicroscopy two hours, 24 hours and one week after rtPA application. Serial visual acuity and intraocular pressure (IOP) were taken pre and one-week post rtPA application. Injection of rtPA effectively caused fibrinolysis in all the cases presented. Conclusion: Fibrinolysis after cataract surgery with conventional topical medications can be time consuming and less efficient. Intracameral application of 25 μg rtPA is an efficient management of fibrin reaction in cataract surgery. Abbreviations: rtPA = recombinant tissue plasminogen activator, IOP = intraocular pressure, BCVA = best corrected visual acuity, PCIOL = posterior chamber intraocular lens.