Summary Interleukin‐33 ( IL ‐33) has been a focus of study because of its variety of functions shaping CD 4 + T‐cell biology. In the present work, we evaluated the modulatory effect of IL ‐33 on suppressor cells in an in vivo transplantation model. C57 BL /6 wild‐type mice were grafted with syngeneic or allogeneic skin transplants and treated with exogenous IL ‐33 daily. After 10 days of treatment, we analysed draining lymph node cellularity and found in allogeneic animals an increment in myeloid‐derived suppressor cells, which co‐express MHC ‐ II , and become enriched upon IL ‐33 treatment. In line with this observation, inducible nitric oxide synthase and arginase 1 expression were also increased in allogeneic animals upon IL ‐33 administration. In addition, IL ‐33 treatment up‐regulated the number of Foxp3 + regulatory T (Treg) cells in the allogeneic group, complementing the healthier integrity of the allografts and the increased allograft survival. Moreover, we demonstrate that IL ‐33 promotes CD 4 + T‐cell expansion and conversion of CD 4 + Foxp3 − T cells into CD 4 + Foxp3 + Treg cells in the periphery. Lastly, the cytokine pattern of ex vivo ‐stimulated draining lymph nodes indicates that IL ‐33 dampens interferon‐γ and IL ‐17 production, stimulating IL ‐10 secretion. Altogether, our work complements previous studies on the immune‐modulatory activity of IL ‐33, showing that this cytokine affects myeloid‐derived suppressor cells at the cell number and gene expression levels. More importantly, our research demonstrates for the first time that IL ‐33 allows for in vivo Foxp3 + Treg cell conversion and favours an anti‐inflammatory or tolerogenic state by skewing cytokine production. Therefore, our data suggest a potential use of IL ‐33 to prevent allograft rejection, bringing new therapeutics to the transplantation field.