Objective To construct the nude mice models infected with Candida albicans and Cryptococcus neoformans. Methods Nude mice infected with Candida albicans and Cryptococcus neoformans respectively were constructed by abdominal injection. The toxic effect and distribution of death rate of nude mice were recorded and pathological examination performed.LD_ 50 was measured by Karber's method; and splenic NK cell activity was also measured. Results Acute toxicities of the nude mice infected by Candida albicans and Cryptococcus neoformans respectively were observed, and these data showed that LD_ 50 of nude mice infected by Candida albicans through abdominal injection was 1.6×107 cfu /ml; LD_ 50 of nude mice infected with Cryptococcus neoformans through abdominal injection was 2×107 cfu /ml.The level of splenic NK cells activities decreased after the nude mice infected by Candida albicans and Cryptococcus neoformans, respectively. Conclusions Models of nude mice infected with Candida albicans and Cryptococcus neoformans respectively are constructed successfully which provide valuable tool for research study of humoral immunity reacting to Candida albicans and Cryptococcus neoformans infection while the cellular immunity is deleted.