Peri-pancreatic fluid collections are late complications of acute pancreatitis. Loculated peri-pancreatic fluid collections, even rare, remain the "black sheep" in terms of drainage, due to difficulty to puncture all compartments, thus prohibiting proper drainage of all compartments. Recombined tissue plasminogen activator (r-tPA) has been advocated as treatment of the loculated collections, due to its ability to dissolve the fibrinous strands and thus facilitate proper drainage. We report the case of a 58 years-old male presenting with a painful loculated peri-pancreatic fluid collection secondary to acute pancreatitis. We performed Alteplase injection, followed by successful endosonographic drainage with lumen apposing metal stent of the collection after 48 hours. Our observation suggests that r-tPA could be a new strategy for loculated collections management, ensuring better drainage and limiting the indication for surgical treatment.