The fermentation of chickpea with immobilized Bacillus natto was optimized to provide references for the further using and industrial production. The fermentation of chickpea with immobilized Bacillus natto (natto-chickpea) was optimized and the effect on thrombolytic activity was studied by the single factor experiments. The result showed that the species of immobilized matrix, matrix concentration, calcium chloride concentration, concentration of Bacillus natto and bead diameter had significant effects on the thrombolytic activity of natto-chickpea. The optimal immobilization conditions were: concentration of sodium alginate 7%(W/V), concentration of calcium chloride 2.5%(W/V), concentration of Bacillus natto 7.4 log cfu/mL, alginate bead diameter 5 mm. Under this optimal condition, the alginate bead has a very high reusability. The process was optimized by single factor experiments which improved highly the thrombolytic activity. The method is of feasibility and can be extended in production.