Objective Through artificial infection with egg drop syndrome virus ( EDSV), to observe theproliferation and dynamic changes of the distribution of EDSV in vivo in different mouse strains, and to provide a theoreticalbasis and data support for construction of the virus vectors. Methods Three mouse strains with different immune status,BALB/ c (normal immunity), Nu (T-cell immunodeficiency) and NSG (high immunodeficiency) mice were used. Thirtytwo5-6 week old female mice per strain were grouped. The mice were infected by intraperitonealy injection of EDSV andserum samples were collected 1, 3, 5, 7, 14, 21, 28 and 35 days later. Antibodies were monitored by an indirect ELISA.Samples of the heart, lung, liver, spleen, kidney, small intestine, uterus, trachea, esophagus and brain were collectedfrom the mice at 1, 7, 14,21 and 28 days after infection. The viral load in each tissue was detected by quantitativefluorescence PCR and comparative Ct (2-ΔΔCT ) method. Results Antibodies were detected 3 days after infection in thesera of BALB/ c mice, reached the highest level at 14 days, and this level was maintained until 35 days. Antibodies weredetected in the Nu mice 3 days post-infection, (but at a lower level than that in BALB/ c mice), the levels were reducedafter 14 days of infection and maintained at a low level until 35 days post-infection. The antibody of NSG mice was negativeduring the whole process of infection monitoring. Relative quantification of nucleic acids showed that EDSV expression inthe liver tissue of BALB/ c mice reached 5. 45 orders of magnitude at 1 day after infection, followed by the spleen,esophagus, uterus, small intestine, lung, trachea, kidney and heart. EDSV content in the brain tissue was the lowest. Withthe extension of infection period, EDSV expression in each tissue was lower than that on the first day of infection, andEDSV expression in the liver and spleen remained high 28 days after infection. Nu mice and NSG mice showed the highestEDSV expression in the spleen 1 day after infection (3. 95 and 4. 05 orders of magnitude, respectively), followed by that inthe liver. Positive signals could be detected in the organs of Nu mice and NSG mice 28 days after infection. EDSVexpression in the liver and spleen remained high. Conclusions EDSV can stimulate immune response in mice, and thelevel of antibody expression in immunodeficient mice is low. EDSV exhibites hepatic and splenic tropism in mice in vivo.The present study provides reference data for development of EDSV vectors, as well as for their further application in laboratory animals.