Objective: To establish a rabbit middle cerebral artery (MCA) embolic stroke model, and to study intra-arterial thrombolysis with recombinant staphylokinase (r-Sak) in this model. Methods: Fifteen rabbits were subjected to a model of RMCA embolic stroke by injected autologous clots into the right internal carotid arterial. Thirty minutes after embolization, the rabbits were treated with saline, r-Sak 0.4 mg/kg or urokinase (UK) 4×104 IU/kg intra-arterial. Digital subtraction angiograms were performed every thirty minutes. Results: RMCA were reopened 100%after injection of r-Sak vs 40%reopened after injection of UK (P<0.01). The ischemia and neurological impairment in both groups were limited. UK prolonged thromb in time, kaolin prothrombin time and prothrombin time, decreased fibrinogen whereas r-Sak did not influence these factors. Conclusion: In the rabbit model of MCA embolic stroke, r-Sak is fibrin-specific and is more effective in lysing embolic clots than UK.