Carboxymethyl chitosan(CMC) was prepared by reacting of chitosan with chloroacetic acid. The structure of CMC was characterized by Fourier transform infrared spectrum (FTIR), nuclear magnetic resonance spectrum (1HNMR), environmental scanning electron microscope (ESEM) and X-ray diffraction (XRD). In addition, the effects of chloroacetic acid dosage, lye concentration, alkalization time, and reaction temperature on the O-substitution degree (O-DS,Y1) and N-substitution degree(N-DS,Y2) were investigated. Furthermore, on the basis of single factor experiment, the corresponding technological parameters were optimized by using the BBD mathematical model in Box-Behnken experimental principle of response surface methodology (RSM). It was found that that the optimal processing for the preparation of carboxymethyl chitosan were as follows: chloroacetic acid dosage 5.71 g, lye concentration(NaOH) content 54%, alkalization time 7h, and the reaction temperature 40℃. The products has highest DS, Y1=72.13%,Y2=28.57%. In comparison with predictive results of the regression model, the relative error is only 0.22% and 0.26%. respectively.