The chemical stability of cefixime was determined by high-performance liquid chromatography (HPLC) under different conditions, including factors such as pH, solvents, initial concentration, temperature and additives. The degradation process follows the first-order kinetics. A pH-rate profile exhibits the U-shape and shows the maximum stability of cefixime at pH = 6. The stability in different pure solvents is ranked as acetone > ethanol > methanol > water, while the degradation rate of cefixime exists a maximum at the ratio of 0.6 in water + methanol mixtures. In addition, the degradation rate increases with the temperature increasing and the activation energy of degradation was found to be 27.078 kJ.mol(-1) in acetone + water mixed solvents. The addition of different additives was proven to either inhibit or accelerate the degradation. The degradation products were analyzed using HPLC, LC-MS and infrared spectroscopy, and the possible degradation pathways in acid as well as alkaline environment were proposed to help us understand the degradation behavior of cefixime. (C) 2017 The Chemical Industry and Engineering Society of China, and Chemical Industry Press. All rights reserved.