Abstract: OBJECTIVE To establish a high performance size exclusion chromatography(HPSEC) method for the determination of the polymers in cefixime granules. METHODS HPLC was used by using TSKgel G2000 SW_XL(7.8 mm×300 mm, 5 μm). The mobile phase was phosphate buffer-acetonitrile(95:5). The flow rate was 0.6 mL·min^-1, the column temperature was 20℃, the detection wavelength was 254 nm, the injection volume was 20 μL. RESULTS The polymers could be separated from cefixime well. The accessories made no interference. The linear of cefixime was within 0.153-20.635 μg·mL^-1(r=0.999 9). The limit of detection was 0.05 μg·mL^-1, and the limit of quantification was 0.15 μg·mL^-1. The repeatability(RSD=0.5%) and intermediate precision(RSD=1.4%) were fine. The sample solution and reference solution were stable at 25℃ within 24 h. The robustness was well, when the flow rate, column temperature and mobile phase ratio were adjusted slightly, the result would not be affected. CONCLUSION This method is simple, robust, sensitive and repeatable. It can be used for quality control of the polymers in cefixime granules.