Amebiasis is an infectious disease caused by Entamoeba histolytica, an anaerobic protozoan parasite, and is a major public health problem worldwide, particularly in areas with inadequate sanitation and poor hygiene. Th1 responses, represented by interferon gamma (IFN-γ), play a protective role by clearing ameba from the gut, while Th2 responses are responsible for the chronic infection. Th17 responses pre-conditioned by the vaccination or by modulating intestinal microbiome are responsible for the protection of mice from the settlement of Entamoeba histolytica. However, the role of interleukin-17A (IL-17A) that is upregulated during the natural course of intestinal amebiasis has not been clarified. The aim of this study was to investigate the role of IL-17A during intestinal amebiasis using a mouse model. IL-17A knockout and wild-type CBA/J mice were intra-cecally challenged with 2×106 E. histolytica trophozoites and infection, pathology and immune responses were monitored. Neither initial settlement of E. histolytica nor inflammation in the ceca was affected in the absence of IL-17A by week 1, but the infection rate and parasite burden declined at a late stage of infection, which was accompanied by an increased IFN-γ/IL-4 ratio. Thus, IL-17A contributes to the persistence of Entamoeba histolytica and modulation of immunity such as IFN-γ/IL-4 ratio, which may be responsible for the reduction of parasite burden in IL-17A KO mice during the chronic phase of intestinal amebiasis.