Exposure to certain engineered nanomaterials has been associated with pathological changes in animal models raising concerns about potential human health effects. MWCNT have been reported to activate the NLRP3 inflammasome in vitro, correlating with lung inflammation and pathology, in vivo. In this study, we investigated the role of IL-1 signalling in pulmonary inflammatory responses in WT and IL-1R-/- mice after exposure to MWCNT. The results suggest that MWCNT were effective in inducing acute pulmonary inflammation. Additionally, WT mice demonstrated significant increased airway resistance 24 h post exposure to MWCNT, which was also blocked in the IL-1R-/- mice. In contrast, by 28 days post exposure to MWCNT, the inflammatory response that was initially absent in IL-1R-/- mice was elevated in comparison to the WT mice. These data suggest that IL-1R signalling plays a crucial role in the regulation of MWCNT-induced pulmonary inflammation.