Inflammation is a prominent feature of renal ischemia-reperfusion (IR) injury characterized by leukocyte infiltration and renal tubular injury. Although invariant natural killer T (iNKT) cells are known for their deleterious role during renal IR injury, the signals that initiate their recruitment and functions in this inflammatory situation remain poorly understood. Assuming on the one hand that alarmin release by necrotic cells during IR injury may be critical (Thierry et al., 2014) and on the other hand that the alarmin IL-33 targets iNKT cells (Bourgeois et al., 2009&2011), we hypothesized that IL-33 might play a part in kidney IR injury by recruiting iNKT cells. Here, we addressed this issue by using C57BL/6 mice lacking IL-33 (IL-33^Gt/Gt). Induction of IR injury was performed by unilateral clamping of the renal pedicle for 32 min after contralateral nephrectomy. We observed release of IL-33 shortly after kidney IR concomitantly with an increase in IL-33 plasma levels within one hour of reperfusion. Compared to wild-type control mice, IL-33-deficient mice exhibited reduced renal IR-induced injury, as was attested by function preservation, reduced histological change and attenuation of neutrophil recruitment. This was associated with the loss of IFN-γ/IL-17A-producing iNKT cell recruitment. Yet, even though iNKT cell-deficient (Jα18KO) mice were protected against IR injury, their circulating IL-33 continued to be increased in this experimental setup similarly to that of their wild-type counterparts. This finding, along with the in vitro observation that IL-33 targets iNKT cells by inducing both IFN-γ and IL-17A led us to put forward the hypothesis that endogenous IL-33 contributes to kidney IRI by promoting iNKT cell recruitment and cytokine production, resulting in neutrophil infiltration and activation at the injury site. This study supports the notion that the IL-33/iNKT cell axis represents a new general physiopathological mechanism involved in sterile inflammation associated with tissue damage.