Background: Around 15-20 % of patients suffering from parapneumonic effusion their condition is complicated by empyema. Despite treatment using aggressive antibiotics, it is associated with significant morbidity and mortality. Drainage of the collection in early stage by intercostal tube with administration of proper antibiotics according to the culture and sensitivity is considered the cornerstone of treatment. Intrapleural fibrinolytics as streptokinase is gaining more popularity. Objective: This study aimed to show the advantages of adding streptokinase to the protocol of conservative management of empyema by studying its effectiveness and safety. Patients and Methods: Our study was conducted on 58 patients on retrospective analytical manner through the period from December 2017 to March 2021 at Kasr Alainy Hospitals. All patients in this study were complaining of empyema following pneumonia. The diagnosis was based on frank pus aspiration from the pleural collection appeared on chest radiography (X-ray, ultrasonography or CT), confirmed by the results of bacteriological culture and gram staining of retrieved samples. Those patients received intrapleural instillation of streptokinase. Results: Mean age of patients was 49. 2 years. The majority of them were males (n=42, 72. 4 %) and females were 16(27. 6 %). According to the causative organisms, Staphylococcus aureus was the commonest (n=31), kleibsiella (n=6), E. coli (n=5), pseudomonas (n=3), mixed (n=2) and others (n=2). Successful treatment occurred in 43 patients (74.1%), partial success in 13 patients (22.4%) and failure of treatment in 2 patients (3.5 %). Conclusion: In our study, intrapleural instillation of fibrinolytics was a safe and effective procedure in management of empyema with decreased incidence of surgical referral.