Background: Group 2 innate lymphoid cells (ILC2s) promote allergic inflammation by producing interleukin-4 (IL-4), IL-5, IL-9, and IL-13. IL-18 can promote T helper 2 cell (Th2) response by inducing IL-4, and IL-13 production from mast cells and basophils. However, the regulation of IL-18 on ILC2s remained unknown. Objective: To investigate the regulatory role of IL-18 in inducing the type 2 innate lymphoid cells. Methods: Twenty patients with allergic rhinitis (AR) and 20 controls were enrolled. The mRNA and protein levels of IL-18 in serum, as well as the frequencies of ILC2 in peripheral blood mononuclear cells (PBMCs) were measured by real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry. The ILC2s were sorted and the mRNA expression of IL-18 receptor in ILC2 was analyzed by real-time PCR. The effects of IL-18 on the proliferation and type 2 cytokine production were detected by tritiated thymidine incorporation test, real-time PCR, and ELISA, respectively. Results: The levels of IL-18 mRNA and protein were significantly higher in AR patients than in the controls (P<0.05). The frequency of ILC2 in peripheral blood was elevated in the AR patients than in the controls. After stimulation by IL-18 and house dust mite (HDM), the expression of IL-18 receptor (IL-18R) by ILC2 was significantly up-regulated. The tritiated thymidine incorporation results showed that IL-18 promoted the proliferation of ILC2 in a dose-dependent manner. IL-18 also induced the expression of IL-5 and IL-13 proteins by ILC2. Conclusion: Our results confirmed -for the first time- the effect of IL-18 in innate immunity, which was demonstrated by direct effect on the differentiation and function of ILC2.