A complex co acervation method was applied to microencapsulate killed vaccine against grass carp hemorrhage by using sodium alginate and chitosan as the wall materials. The single factor test and the orthogonal experiments were conducted to optimize the conditions of preparing the microcapsules. The optimal conditions were as follows: 1.5% sodium alginate, 1% chitosan, 4% calcium chloride and 2mL inactivated vaccine. The influence of factors that affect encapsulation efficiency was sodium alginate concentration > vaccine dosage > chitosan concentration > calcium chloride concentration. The microcapsules have an average diameter of （7.02±3.95）μm, the average encapsulation rate is 60.53% and the average drug loading rate is 8.12 mg/g. The microcapsules have good release properties in PBS (pH 7.4) and saline solution.