Objectives: To evaluate the effectiveness of intrapleural injection of streptokinase as a method of treatment for cases of loculated empyema thoracis that do not drain well with insertion of intercostal tube. Patients & Methods: The study included 25 patients with loculated empyema that do not drain well with insertion of intercostal tube. 250.000 units of streptokinase are injected intrapleural via the chest tube. The chest tube is clamped for 3 hours. The chest tube de-clamped to drain in the under-water seal. The procedure repeated for another 2 days, for a total of 3 successive days. Results: the study included 16 males (64%) and 9 females (36%), The duration of pleural drainage ranged from 4-12 days, with mean (SD) of 6.12 (±1.81), and the amount of total drainage ranged from 300- 2150 ml, with a mean (SD) of 942 ml(±538.45), The cause of empyema in this study was not defined in (3) 12% of cases, complicated para-pneumonic effusion in (11) 44% of cases, post-traumatic in 10 (40%) of cases and post-operative in (one) 4% of cases,. The results of the procedure were successful in 16 cases (64%) and failed in 9 (36%) cases. Conclusion: Loculated empyema thoracis that do not drain well with insertion of intercostal tube, intrapleural injection of streptokinase in a dose of 250.000 units once daily for three successive days is an effective method of adjunctive treatment, and may avoid the need of open thoracotomy for decortication.