Chlorogenic acid (CGA) is a phenolic acid that has a wide range of pharmacological effects. However， the protective effects and mechanisms of CGA on liver fibrosis are not clear. This study explored the effects of CGA on miR-21-regulated TGF-β1/Smad7 liver fibrosis in the hepatic stellate LX2 cell line and in CCl4-induced liver fibrosis in Sprague-Dawley rats. The mRNA expression of miR-21， Smad7， connective tissue growth factor (CTGF)， α-smooth muscle actin (α-SMA)， tissue inhibitor of metalloproteinase 1 (TIMP-1)， matrix metalloproteinase-9 (MMP-9)， and transforming growth factor-β1 (TGF-β1) and the protein levels of Smad2， p-Smad2， Smad3， p-Smad3， Smad2/3， p-Smad2/3， Smad7， CTGF， α-SMA， TIMP-1， MMP-9 and TGF-β1 were assayed in LX2 cells and liver tissue. The effects of CGA after miR-21 knockdown or overexpression were analyzed in LX2 cells. The liver tissue and serum were collected for histopathological examination， immunohistochemistry (IHC) and ELISA. The mRNA expression of miR-21， CTGF， α-SMA， TIMP-1， and TGF-β1 and the protein expression of p-Smad2， p-Smad3， p-Smad2/3， CTGF， α-SMA， TIMP-1， and TGF-β1 were inhibited by CGA both and . Meanwhile， CGA elevated the mRNA and protein expression of Smad7 and MMP-9. After miR-21 knockdown and overexpression， the downstream molecules also changed accordingly. CGA also lessened the degree of liver fibrosis in the pathological manifestation and reduced α-SMA and collagen I expression in liver tissue and TGF-β1 in serum. CGA might relieve liver fibrosis through the miR-21-regulated TGF-β1/Smad7 signaling pathway， which suggests that CGA might be a new anti-fibrosis agent that improves liver fibrosis.