T(H)17 cells have been implicated in a growing list of inflammatory disorders. Antagonism of T(H)17 cells can be used for the treatment of inflammatory injury. Currently, very little is known about the natural compound controlling the differentiation of T(H)17 cells. Here, we showed that Baicalin, a compound isolated from a Chinese herb, inhibited T(H)17 cell differentiation both in vitro and in vivo. Baicalin might inhibit newly generated T(H)17 cells via reducing RORγt expression, and together with up-regulating Foxp3 expression to suppress RORγt-mediated IL-17 expression in established T(H)17 cells. In vivo treatment with Baicalin could inhibit T(H)17 cell differentiation, restrain T(H)17 cells infiltration into kidney, and protect MRL/lpr mice against nephritis. Our findings not only demonstrate that Baicalin could control T(H)17 cell differentiation but also suggest that Baicalin might be a promising therapeutic agent for the treatment of T(H)17 cells-mediated inflammatory diseases.