We evaluated ex and in vivo effect of streptokinase on pancreatic necrosum to improve the success rate of pigtail catheter drainage and irrigation in infected walled off pancreatic necrosis using step up approach and also looked at potential risk of bleeding.1000 IU/ml of streptokinase was added to 10 g. of intra-operatively obtained fresh tissue of peripancreatic necrosis and results compared to treatment with saline. Mixture was incubated for 12 h in thermostat at 37.5 °C and subjected to histopathology. Subsequently streptokinase (50,000 units thrice a day for 5 days through PCD) was used in two patients with walled off pancreatic necrosis (WOPN) not responding to step up approach and who were being considered for surgery.Grossly there was fragmentation of necrosum in streptokinase treated tissue. Microscopically complete loss of supportive collagenous framework was noted in streptokinase treated necrosum with clumping of necrotic tissue into structure-less mass. No such changes were discernible in saline treated tissue. In two patients with WOPN there was clearance of debris after streptokinase instillation. None of the patients was on thromboprophylaxis and bleeding was not noticed in any of the patients.Based on ex vivo effect of streptokinase in dissolution of necrosum at periphery, we believe that in patients with walled off pancreatic necrosis (WOPN) not responding to pigtail catheter drainage and saline irrigation; streptokinase may prove to be useful adjunct.