Fibrinolytic drugs are widely used for the management of atherothrombotic diseases such as acute or prior myocardial or cerebral infarction, ischemic stroke and venous thromboembolism. Quite a lot of in vitro models have been developed to study clot lytic activity of fibrinolytic drugs, but all of these have certain limitations. There is need of a rapid method to check and quantify the clot lytic efficacy of fibrinolytic drugs precisely. In the present study, an attempt has been made to curtail two novel methods to study fibrinolysis in a simplified and easy way using standard fibrinolytic dugs, plasmin and streptokinase. Fibrin clots were allowed to form in microcentrifuge tubes using plasma separated from the whole blood from healthy mice or directly using fibrinogen and thrombin. After lysis by various doses of plasmin and streptokinase, fluid was removed and its volume was measured. Difference obtained in volume taken before and after plasma clot lysis was expressed as percentage of fibrinolysis. The validity of new-fangled methods was assessed by using various concentrations of standard drugs plasmin and streptokinase as positive control and water as negative control. The results appear to validate their claim by demonstrating a dose-dependent effect of standard test samples. The IC50 values for both the drugs were also found out when accessed by plasma clot lysis and fibrin clot lysis method. Thus the novel methods presented here could be reproducible, instant, quantitative, accurate, cost effective and valuable models to study fibrinolytic effect of newly developed drugs as well as known drugs. Test drugs can also be analyzed in the same way using presented methods.