Objective To establish the model of human chimeric mouse infected by HBV through using human cord blood stem cell. Methods Human cord blood stem cells were twice injected through tail vein into the body of each nude mouse. Hepatic tissues were get at the 7th，14th and 21th days to test the growth of human hepatic cells by AFP immunohistochemistry. In addition，mice were infected by HBV to quantitively test the serum AFP and ALB by RIA.Results The mouse hepatic AFP，existing in the cytoplasm，could express continuously. AFP positive cells could be observed at the 7th，14th and 21st days. Meanwhile，the infected mouse hepatic tissues showed HBsAg positive by immunohistochemistry. It showed significant difference (P < 0. 05) between experimental and control groups. Conclusions Human cord blood stem cells can be transplanted into mouse liver and differentiate into human hepatic cells which are able to survive and to be infected by HBV in chimeric form.