Abstract: Objective To study the different effects of recombinant nattokinase （r-NK） on coagulation and fibrinolysis system in Beagle dogs and in miniature swine when trqated repeatedly at large dosage. Methods Platelet-related parameters were obtained by blood analyzer. The fibrinogen （Fib）, activated partial thrombin time （APTT），prothrombin time （PT） and thrombin time：（TT） were determined by coagulation method with the coagulation detector. Plasmmogen （PLG） and tissue-type plasminogen activator （t-PA） were tested by ELISA. Results Repeated administration presented the same blood vessel irritation both in Beagle dogs and miniature swine. After 1 week of administration, the number of platelets was decreased, PT was prolonged, Fib concentration decreased and the activity of PLG were increased in Beagle dogs. However, r-NK had no effects on the above parameters in miniature swine. Conclusion There was toxic difference between different animals towards r-NK at the same dosage. In Beagle dogs, r-NK could break the balance between the coagulation and fibrinolysis system. Whereas r-NK had no effects on the coagulation and fibrinolysis system in miniature swine.