Abstract: Under the conditions of alkaline and heating, cefoperazone sodium could be degraded to two sulfhydryl compounds (R'SH and R″SH). At pH 4.4, Cu(Ⅱ) was reduced to Cu(Ⅰ) by R'SH and then generated leucosol with R″SH, which leaded to the resonance scattering signal (RSS) increase drastically. Based on this fact, a method of resonance scattering spectroscopy for determination of cefoperazone sodium was proposed. The optimized conditions found were as follows:1 concentration of sodium hydroxide solution:0.20 mol·L^-1; 2 degradation time of cefoperazone sodium:40 min; 3 amount of HOAc-NaOAc buffer solution at pH 4.4:1.00 mL; 4 amount of 5.00 mmol·L^-1 Cu(Ⅱ):0.50 mL; 5 time of reaction:2 min. Linear relationship was obtained between enhanced RSS intensity (ΔI_RSS) and concentration of cefoperazone sodium in the range of 0.02 to 2.40 mg·L^-1, with detection limit (3s/k) of 0.006 2 mg·L^-1. The proposed method was applied to the determination of cefoperazone sodium in injection, giving results of recovery in the range of 97.5% to 103%. Values of RSDs (n=5) found were in the range of 2.0% to 2.6%.