NKT cells are a subset of lymphocytes that reacts to glycolipids presented by CD1d. Invariant NKT cells (iNKT) correspond to more than 90% of the total population of NKTs and reacts to α-Galactosylceramide (αGalCer). αGalCer promotes a complex mixture of Th1 and Th2 cytokines, as IFN-γ and IL-4. NKT cells and IFN-γ are known to participate in some models of renal diseases, but further studies are still necessary to elucidate their mechanisms. The aim of our study was to analyze the participation of iNKT cells in an experimental model of tubule-interstitial nephritis. We used 8-week-old C57BL/6j, Jα18KO and IFN-γKO mice. They were fed a 0.25% adenine diet for 10 days. Both adenine-fed WT and Jα18KO mice exhibited renal dysfunction, but adenine-fed Jα18 KO mice presented higher expression of KIM-1, TNF-α and type I collagen. To analyze the role of activated iNKT cells in our model, we administered αGalCer in WT mice during adenine ingestion. After αGalCer injection we observed a significantly reduction in serum creatinine, pro-inflammatory cytokines and renal fibrosis. However, this improvement in renal function was not observed in IFN-γKO mice after αGalCer treatment and adenine feeding, illustrating that this cytokine plays a role in our model. Our findings may suggest that IFN-γ production is one of the factors contributing to improved renal function after αGalCer administration.