Management of an early empyema is an important problem in thoracic surgery. As an alternative to surgical treatment empyema is in patients who developed early empyema , intra-pleural fibrinolysis has been used with favorable results. This modality of treatment may reduce known morbidities secondary to surgical procedures and may result in significant medical cost savings. Aim of the study is to test the efficacy and safety of tissue plasminogen activator and Streptokinase for management of early empyema. Patients and Methods: our study included 48 patients presented with complicated parapneumonic effusion and early empyema . Patients were divided into two groups each contains 24 patients. First group treated with intra-pleural Alteplase (tissue plasminogen activator) and the second group treated with streptokinase, both were instilled via an intercostal chest tube. Clinical and radiologic (chest radiographs (CXR) and chest computed tomography (CT) data used for evaluation of efficacy of both protocols. Results: tissue plasminogen activator give excellent results in early empyema , it showed success rate 100% , dramatic improvement in both chest tube drain and pleural thickness with no need for further surgical intervention, Streptokinase showed success rate 83.4% in comparison to TPA. Conclusion : Intrapleural tissue plasminogen activator is safe and more efficient than Streptokinase as a chemical modality in treating patients presented with complicated pleural effusion and early empyema.