Direct injection of a fibrinolytic agent to the intra-arterial thrombosis may increase the effectiveness of thrombolysis by enhancing the permeation of thrombolytic agents into the blood clot. Permeation of fibrinolytic agents into a clot is influenced by the surface pressure, which is determined by the injection velocity of fibrinolytic agents. Computational fluid dynamic methods were used in order to predict clot lysis for different jet velocities and nozzle arrangements. Firstly, thrombolysis of a clot was mathematically modeled based on the pressure and lysis front velocity relationship. Direct injection of a thrombolytic agent increased the speed of thrombolysis significantly and the effectiveness was increased as the ejecting velocity increased. The nine nozzles model showed about 20% increase of the lysed volume, and the one and seventeen nozzles models did not show significant differences. Secondly, thrombolysis was modeled based on the enzyme transport and the fluid flow equations, and quasi steady numerical analysis was performed. Clot lysis efficiency was also increased as injection velocity increased.