Abstract:[Background] Environmental estrogens, major components in the new types of environmental pollutants, threaten the health of humans and animals by their adverse effect on the functions of the endocrine system. Microbial degradation is considered an efficient method in the removal of estrogenics and the bioremediation of polluted environments. [Objective] To improve diethylstilbestrol (DES) biodegradation efficiency, we studied the degradation characteristics of a DES-degrading bacterium Serratia sp. AXJ-M. [Methods] The degradation conditions of DES by Serratia sp. AXJ-M were optimized by performing the single factor test, Plackett-Burman test, steepest ascent hill climb test, and Box-Behnken test. [Results] Application of (NH4)2SO4, ZnCl2, and tryptone as inorganic nitrogen sources, additional metal ions, and added nutrients, respectively, significantly promoted the degradation of DES. The concentration of ammonium sulfate and DES and pH value were selected as the key parameters affecting the degradation of DES by performing the Plackett-Burman experiment. Box-Behnken experiment design and response surface methodology (RSM) analysis were adopted, the optimized conditions were (NH4)2SO4 1.48 g/L, ZnCl2 0.02 g/L, culture temperature 30℃, pH 7.19, DES 119.5 mg/L, and inoculation biomass 3%. The degradation rate of DES under these conditions reached 76.89% within 7 d, which was 17.38% higher than initial conditions. [Conclusion] Serratia sp. AXJ-M, a highly efficient DES degrading strain, can be used as an excellent microbial resource for bioremediation of the environment polluted by DES or other synthetic estrogens.