【Abstract】 Objective To generate and identify the AD model heterozygous mice by hybridization with the mice over-expression of Slit2 protein, for the research of the role of the over-expression of Slit2 protein on AD at the whole animal level. Method The heterozygous Tg2576 transgenic mice was generated and identified. The positive offspring were mated with Slit2-Tg homozygous mouse, which Slit2 protein was over-expression . The gene type of the offspring express were identified. Results The generation of the Tg2576 heterozygous mice and Slit2-Tg mice were successful and Tg2576 /- mouse were identified. 5 Tg2576 /-;Slit2-Tg mouse were acquired through mating Tg2576 /- mouse to Slit2-Tg mouse. Conclusion Generation of Slit2 protein over-expression heterozygous mice by hybridization with AD model heterozygous mice was successful, which can supply a novel animals model for further research of the Slit2 protein over-expression on AD．