IL-33, a member of the IL-1 family of cytokines, has been shown to activate NF-kB and MAP kinase family through the IL-1 receptor-related protein, ST2L (or IL-33R). We have previously reported that TRAF6 is a critical signal transducer in IL-33 signaling pathway, demonstrating the critical involvement of TRAF6 in IL-33-mediated p38, JNK and NF-kB activation. In addition, we found that IL-33 rapidly activated a tyrosine kinase, JAK2, and demonstrated the functional involvement of JAK2 in IL-33-induced IkBa degradation and NF-kB activation, since a JAK2 inhibitor, AG490, effectively inhibited this signaling pathway. In these studies, we employed murine wild-type fibroblast cells and TRAF6-deficient or JAK2-deficient MEFs. Here, we employed murine bone marrow-derived mast cells (BMMC) as IL-33-responding cells important in the allergic responses, and examined whether fullerene derivatives have inhibitory effects on these cells. BMMC when stimulated with IL-33 (10ng/mL) exhibited IL-6 and IL-13 mRNA expression and production. In this system, the bis-malonic acid fullerene derivative significantly inhibited IL-33-induced expression of IL-6 but to the lesser extent of IL-13. In addition, bis-malonic acid fullerene inhibited significantly the IL-33-induced IkBa degradation and IKKb activation, followed by the NF-kB activation. However, bis-malonic acid fullerene derivative has no effect on the expression of IL-33 adaptor molecules including IL-1RAcP, MyD88, IRAK1 or TRAF6 and ST2L. Further, neither the activation of p38 MAPK, ERK1/2 MAPK or JNK1/2 was not affected by this fullerene derivative. While how the fullerene derivative binds and inhibits IKKb activation is to be investigated, inhibitory drugs specific to the IKKb leading to NF-kB activation is of great interest in terms of the regulation of inflammatory responses and allergic responses.