Candida albicans is a commensal fungus that commonly colonizes human mucosal surfaces. When the host immune defenses are impaired, C. albicans triggers recurrent infections of the oral mucosa and tongue. We previously reported that the characteristics in NOD/SCID. e2f1(-/-) mice that have naturally decreased saliva and T and B cells that do not develop increase the susceptibility of oral bacterial infection in the oral cavity. Next, we sought to establish a C. albicans infection model in NOD/SCID. e2f1(-/-) mice. C. albicans yeast forms were introduced by wiping a cotton swab moistened with C. albicans solution on the tongue after disinfection by 0.2 Chlorhexidine for the first time. After an interval of 60 min, the inoculation was performed by pipette 2 or 4 times at an interval of 60 min. The number of C. albicans colonized on the tongue significantly increased but there were no significant difference between NOD/SCID. e2f1(+/+) mice and NOD/SCID. e2f1(-/-) mice at 120-240 minutes. However, a significant difference between these mice was observed at 24 hours after the last inoculation. Moreover, 5 inoculations/day were also performed for 2-4 days and significant differences between mice arose, and the maximum level of infection was found at 24 hours after consecutive inoculation for 3, 4 and 5 days, but the levels were reduced after 48 h. It is suggested that the saliva volume and flow are important for preventing 24-hour colonization of C. albicans. NOD/SCID. e2f1(-/-) mice are a relevant mouse model for 24-hour colonization on the tongue.