In the current study, through characterizing the expression and function of Sirt2 in Tregs in a mouse colitis model, we discovered that Sirt2 was highly expressed in lamina propria Tregs and it suppressed Foxp3 expression while preventing Treg polarization toward Th17 cells, probably through downregulating signal transducer and activator of transcription 3 protein rather than reducing Sirt2 messenger RNA (mRNA). This evidence concerns the gene FOXP3 and colitis.