Balamuthia mandrillaris is a causative agent of granulomatous amebic encephalitis, a rare but often fatal condition. To investigate the role of T helper (Th) cell subsets in the immune response against B. mandrillaris, we examined 3 mouse strains with distinct immunological profiles: C57BL/6 (Th1-dominant), BALB/c (Th2-dominant), and ICR (balanced Th1/Th2). Mice were infected intranasally with 1×10⁵ amoebae. Body weight and neurologic symtoms were monitored weekly, and cytokine expression was assessed biweekly over 6 weeks. Minimal weight loss and no mortality were observed in C57BL/6 mice, whereas BALB/c and ICR mice exhibited significant early and delayed mortality, respectively. Interleukin-17A expression was notably elevated in C57BL/6 mice compared with the other strains. These findings indicate that a robust Th17 response, particularly interleukin-17A production, is a critical component of the host defense against B. mandrillaris infection.