Response surface methodology (RSM) was used for controlling molecular weight (MW) and degree of deacetylation (DOD) of chitosan in chemical processing. In a reduced model, MW of chitosan is y = 1736166.406 - 250.745X(1)X(2) - 265.452X(2)X(3), with R( 2) = 0.86, and DOD of chitosan is y = 30.6069 + 0.3396X(1) + 0.4948X(2) + 0.0094X(3)(2), with R( 2) = 0.89. MW of chitosan depends on the crossproduct of temperature and NaOH concentration and the crossproduct of NaOH concentration and time, and DOD depends linearly on temperature and NaOH concentration, and quadratically on time. Chitosan was widely depolymerized in a range from 1,100 kDa to 100 kDa and deacetylated from 67.3 to 95.7% by NaOH alkaline treatment. MW and DOD of chitosan were drastically decreased and increased, respectively, with increase of temperature, reaction time, and NaOH concentration. Furthermore, the rate of MW decrease and DOD increase of chitosan gradually decreased with prolonged reaction time.