Candida albicans (C. albicans), a common pathogenic fungus in nature, has enough capacity to cause severe brain infection through various means under immunocompromised conditions. Currently, establishing a basic animal disease model has become the main research tool, which is conducive to simulating fungal encephalitis effectively. However, the widely used bloodborne infection model established by intravenous (I.V) injection in mice usually results in systemic infections but cannot simulate significant brain inflammation. Here, we developed a fungal encephalitis model by intracerebroventricular (I.C.V) injection of C. albicans to better simulate the significant harm and consequences. Compared with I.V, a greater number of colony-forming units (CFUs) in the brain was induced following I.C.V. Magnetic resonance imaging (MRI) results revealed more obvious inflammation in the external capsule area of the brain. Meanwhile, behavioral experiments with the Y-maze also indicated that abnormal activity behavior further reflected significant short-term memory impairment after I.C.V of C. albicans. In summary, these studies not only provide a novel fungal encephalitis model for understanding the pathogenesis mechanism of this disease but also lay a solid foundation for future effective treatment.