Abstract: There are two traditional methods to build the genetically modified mouse model, one method is to use the microinjection to transfer specific nucleotide sequence into the fertilized eggs or embryos of mouse, while the other is to introduce the embryonic stem cells of mouse into the blastocyst. The first method, that is, nucleic acid transferring method, is widely used which can transfer the nucleic acid through injection method, transfection method and gonadal tissue mediate. The research progress of nucleic acid transferring method in the process of building genetically modified mouse model was summarized including pronucleus injection, blastocyst microinjection, the nucleic acid electrotransfection of fertilized eggs, the nucleic acid electrotransfection of oviduct, sperm-mediated gene transfer, ovarian tissue injection, etc. Then, the further usage and development direction of nucleic acid transferring method were prospected.