Th17 cells play a critical role not only in host defense and mucosal defense but also in tissue inflammation and autoimmunity. Although the mechanism of regulation of Th17 cell differentiation at transcriptional level is extensively studied, little is known about the post-transcriptional gene regulation in Th17 cells. Here we report for the first time that AT-rich interactive domain 5a (Arid5a) controls the differentiation of Th17 cells through stabilization of Stat3 mRNA. Arid5a is specifically induced under Th17 cell polarizing condition but not Th1, Th2, and Treg cell condition. Consequently, enhanced Arid5a protein binds to the stem-loop sequence of the 3’ untranslated region (UTR) of the Stat3 mRNA, in turn, stabilizes Stat3 mRNA by competing with Regnase-1 on the same portion. Conversely, Arid5a deficiency led to reduction of the frequency of Th17 cell population, in which the expressions of the Stat3-regulating gene, Rorc, IL-21, IL-23R was significantly lower than those of WT T cells. Moreover, we have shown that such intrinsic role of Arid5a in T cells is critical for induction of experimental autoimmune encephalomyelitis (EAE) in Rag2 deficient mice by adoptively transferred T cells. Thus, we demonstrated that Arid5a plays an important role in the differentiation of Th17 cells through control of stabilization of Stat3 mRNA, which results in exacerbation of autoimmune inflammation.