Objective To explore the pharmacological effect of acodarin an extract from the Chinese herbal medicine Epimedium in regulating signal transducer and activator of transcription 3 STAT3 -mediated macrophage polarization via exosomes derived from hepatocellular carcinoma HCC cells. Method HepG2 cell line was administrated by Icaritin 10 μmol / L or DMSO in vitro and then was cocultured with THP-1 cell-derived macrophage in a Transwell coculture system. The levels of IL-6 and TGF-β secreted by the macrophage were detected by ELISA assay. Flow cytometry was utilized to examine CD206 expression which is a biomarker of M2 macrophage. We extracted and identified the exosomes derived from DMSO or Icaritin-treated HepG2 cells. ELISA assay was utilized to detect IL-6 and TGF-β expressed in macrophage after administrated with exosomes isolated from HCC cells with or without Icaritin treatment. The expression and activity of STAT3 were assessed by Western blot assay. Result the expression of IL-6 TGF-β and CD206 were increased after cocultured with HCC cells but decreased significantly after cocultured with Icaritin - induced HepG2 cells. Meanwhile Icaritin-induced exosome also inhibited the expression of IL-6 and TGF-β as well as STAT3 activity. Conclusion Icaritin can inhibit macrophage polarize to M2 via HCC cells-derived exosomes. These findings indicate that Icaritin was an immune regulator in HCC microenvironment.