Our data demonstrate that baicalein exerts dose-dependently anti-fibrotic effects against SSc by suppressing TGF-β1- and PDGF-mediated ECM accumulation in vitro as well as alleviating fibrosis, regulating B-cell abnormalities, and attenuating inflammation in bleomycin-induced scleroderma in vivo. Here, TGFB1 is linked to systemic sclerosis.