IL-33 is a multifunctional cytokine in immune regulation that activates Th1 cells, Th2 cells, CD8(+) T cells and NK cells. Our study showed that transgenic expression of IL-33 attenuated tumor metastasis in the B16 melanoma and Lewis lung carcinoma (LLC) metastatic models. The percentages and cytotoxicity of CD8(+) T cells and NK cells and their infiltration into the tumor tissues were significantly increased by the transgenic expression of IL-33 in tumor-bearing mice. Treatment with recombinant IL-33 could also increase the cytotoxicity of CD8(+) T cells and NK cells in vitro. In addition, depletion of CD8(+) T cells and NK cells using anti-CD8 or anti-asialo GM1 antibody abolished the pulmonary metastasis inhibition mediated by IL-33. Furthermore, IL-33 stimulated the activation of NF-κB and increased CD69 expression, which is a marker of the activated form of the two cell subsets, in CD8(+) T cells and NK cells. Our results suggest that IL-33 stimulated NF-κB signaling and promoted the proliferation, activation and infiltration of CD8(+) T cells and NK cells, which resulted in the inhibition of pulmonary metastasis in B16 melanoma and LLC mice models. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.