Abstract: The aims of this study were to explore the feasibility and stability of producing MxA transgenic mice mediated by Type-A spermatogonia in vivo. The pcDNA-MxA plasmid and transfection reagent ExGen500 were suspended and injected into testicle tissue of 7-day-old male ICR mice from 5 different points; the testis-mediated gene transfer(TGT)mice mated with wildtype female mice at different sexual maturity stages(6-, 12- and 24-week-old), to detect the integration and expression of foreign gene in offspring. The mice expressed MxA were chosen for challenge test, health status and respiratory system tissue pathological changes were observed. Detection result of MxA integration by PCR and Southern blot in the F₁-generation mice showed that foreign gene integration rates of 2 TGT mice at different sexual maturity stages(6-,12-, and 24-week-old)were 11.11%(2/18), 11.76%(2/17), 11.54%(3/26) and 13.64%(3/22), 13.33%(2/15), 11.76%(2/17),respectively. The average integration rates in two groups were 11.47% and 12.91%, the difference was not significant(P＞0.05). RT-PCR detection result showed that MxA gene was expressed in 3 of 14 integration mice. Infection challenge test with H5N1 influenza strains results showed that constitutional symptom and pathologic change degree of transgenic mice were more slighter than that of wild-type mice. The results indicated that the method of type-A spermatogonia mediated gene transfer shows bright future for application because it is a feasible and reproducible transgenic approach. MxA transgenic mice have disease resistance to H5N1 subtype avian influenza viruses to some degree.