Amebic liver abscess (ALA) is caused by a protozoan parasite, Entamoeba histolytica (Eh). After direct injection of Eh into hepatic parenchyma, NKT cells and IFN-γ are known to suppress ALA development. Large amount of Th2 cytokines are also produced at early after Eh infection, but the source and function of this initial Th2 cytokines are unknown. Type 2 innate lymphoid cell (ILC2) can produce abundant IL-5 and IL-13. Therefore, we examined whether ILC2 was involved in this early Th2 cytokine production and the pathogenesis of ALA. In newly established ALA model by inoculating Eh via portal vein, C57BL/6 IFN-γ KO mice showed severer ALA with higher number of ameba than wild-type (WT) mice, reiterating the imprtance of IFN-γ for host defense to ameba even after their translocation via natural route. In the setting, the number of ILC2 and those producing IL-5 and IL-13 were significantly increased, suggesting the negative association between ILC2 and IFN-γ in ALA. To examine the impact of ILC2 on ALA formation, we depleted ILC2 in T/B cells deficient Rag2 KO mice using anti-CD25 mAb. In ILC2-depleted Rag2 KO mice, both the number of ameba and ALA development were better controlled than non-depleted mice with significance. These results indicate that ILC2 exacerbates the pathogenesis of ALA and IFN-γ regulates the number and functionof ILC2s in liver.