Background: Parapneumonic pleural effusion needs drainage by small drain or chest tube, but when becomes loculated it needs surgery, which can be avoided by using intrapleural streptokinase (SK).  Objectives: This study aimed to assess the outcome, efficacy and safety of intrapleural streptokinase in management of parapneumonic loculated pleural effusion. Methods: A prospective study through the period from May 2020 to May 2024 included 45 patients presented with parapneumonic pleural effusion in which chest tubes were inserted. Effusion was not fully drained because of septations. Streptokinase was tried in these patients. Our protocol was using 250,000IU in 50 ml normal saline injected intrapleural. The same dose can be repeated every 48 hours to maximum of ten trials. Close observation for pain, anaphylaxis, fever or any complication. Results: There was a highly significant increase in intercostal chest tube (ICT) drainage (p=0.003) after streptokinase injection. Patients had average doses of 4-10 (7.5 ± 1.94). Resolution occurred in 36 patients (80%). Patients under the age of 40 years showed a significantly higher success rate than older patients (p=0.03). There was significant association between starting streptokinase treatment from the beginning of symptoms and resolution (p=0.001). Conclusion: Streptokinase had safe, efficient and good outcome in parapneumonic loculated pleural effusion. The outcome was significantly better in young patients (< 40 years) and in patients started streptokinase in the first ten days of their symptoms.