Parapneumonic effusions caused by an infection of the pleural membranes occur in 40-57% of cases of pneumonia. A variable percentage (10-20%) of parapneumonic effusions progresses to empyema (pus) and/or abscess formation (encapsulation). Pleural infection is associated with significant morbidity and mortality which may be as high as 20-35% in immunocompromised patients Standard treatment of these collections in adults involves antibiotic therapy, effective drainage of infected fluid and surgical intervention if conservative management fails. For parapneumonic effusions which require clearance, appropriate therapy is effective drainage via an intercostal catheter (ICC) with antibiotic therapy. The presence of fibrinous septae in the pleural space, known as loculations, may result in inadequate drainage of effusions and therefore non-resolution of infection and systemic sepsis. Without effective intercostal catheter drainage, surgical intervention (VATS or open) has usually been required to clear loculations for resolution of infection. Non-surgical treatment options to reduce the impact of adhesions and locule include (in addition to appropriate antibiotic therapy) single and multiple thoracocentesis, or single and multiple intercostal tube thoracostomies, with or without intrapleural fibrinolytic agents. Fibrinolytic agents including streptokinase, urokinase, alteplase and recombinant tissue plasminogen activator (rTPA) have been used safely and effectively intrapleurally for complicated pleural effusion and empyema. MIST 2 trial has established intrapleural therapy as the mainstay of CPEE treatment hence avoiding surgery and decreasing the length of hospitalization; however, little is known about the correct dosage needed for tPA and DNase. Dose and duration of intrapleural therapy based on MIST 2 involve multiple dosing and can be time-consuming for health care providers . Previous studies showed that complexity of treatment is a factor associated with poor adherence to a regimen. For this reason, trying to find the minimum effective dose and simplifying the regimen is essential for minimizing side effects and maximizing adherence. The review of currently available literature shows concurrent administration of tPA and DNase to be safe and effective even at lower cumulative dose Other study was carried out in May 2022 in which Modified regimen intrapleural alteplase 16 mg t-PA with 5 mg DNase for total 3 doses that administered sequentially within 24 h had been used. In this study, modified regimen of t-PA and DNase offer an alternative therapeutic option for patients that are unfit or refuse surgical intervention but persistent pleural infection. They have demonstrated similar treatment success comparable to other studies, as evidenced by improvement on pleural fluid drainage and reduction in pleural opacity on day 7 chest x-ray was approximately 50% from the baseline using intrapleural 16 mg t-PA with 5 mg DNase. The mechanism of action of t-PA and DNase in pleural cavity remain unclear. Studies suggested that IPFT may trigger the monocyte chemoattractant protein 1 (MCP-1) pathway which promote pleural fluid formation and subsequently causes a therapeutic lavage effect that increases pleural fluid drainage. Another option for intrapleural therapy may be pleural irrigation with normal saline. The idea behind is to dilute and remove bacteria, cytokines, inflammatory cells, and pro-fibrinogenic coagulation factors, which induce pleural fluid organization. Also, the mechanical process of irrigation increases pleural fluid drainage by reducing stasis and organization of the intrapleural contents . A randomised controlled pilot study in which saline pleural irrigation (three times per day for 3 days) plus best-practice management was compared with best-practice management alone was performed in patients with pleural infection requiring chest-tube drainage. The primary outcome was percentage change in computed tomography pleural fluid volume from day 0 to day 3. Patients receiving saline irrigation had a significantly greater reduction in pleural collection volume on computed tomography compared to those receiving standard care. Significantly fewer patients in the irrigation group were referred for surgery (30). However, till date there is no study done on head to head comparison between intrapleural fibrinolytic with alteplase and DNAse Versus Pleural irrigationwith normal saline.