Abstract: Six compounds were made by chemical synthesis or semi-preparative HPLC separation for azithromycin to promote quality and impurity control. They are erythromycin A 6,9-imino ether, erythromycin A 9, 11-imino ether, 3'-N-demethyl azithromycin, 3'-N-4-(acetylamino)phenylsulphonyl-3'-N-demethyl azithromycin, 3-decladinosylazithromycin and 12-dedeoxyazithromycin (azithromycin B), which were obtained through chemical synthesis or semi-preparative HPLC separation. Their structures are identified by MS, ¹H NMR and ¹³C NMR. The source and control methods of these impurities are also presented to improve azithromycin production process.