In this study, we demonstrate that pharmacological and genetic inhibition of HDAC4 attenuates renal fibrosis and suppresses the molecular mechanisms leading to renal fibrosis, including the pEMT, fibroblast activation, and activation of the TGF-β1/Smad3, STAT3, and ERK1/2 signaling pathways. The gene discussed is MAPK3; the disease is renal fibrosis.