Abstract: Lycium barbarum polysaccharide was extracted by ultra-high pressure,and the response surface methodology(RSM)was used to optimize the process parameters. On the basis of single-factor experiments,pressure,time,temperature and liquid-material ratio were selected as four independent variables. An experimental design was carried out involving four variables at three levels. The antioxidant activity of polysaccharide from Lycium barbarum was further studied. The results showed that the optimum process for extraction of Lycium barbarum polysaccharide by ultrahigh pressure:The extraction pressure 446 MPa,extraction time 8 min,extraction temperature 58℃,liquid-material ratio 23:1 mL/g,the estimated and observed values of maximal yield of polysaccharide was 9.54% and 9.52%,respectively.The relative error was 0.21%.The results showed that the antioxidant activity of polysaccharide showed a dose-dependent manner within the range of 0~1.0 mg/mL,and the scavenging activities of ·OH and O₂^-· reached 76.98%±2.64% and 73.02%±1.83%,respectively,when at concentration of 1.0 mg/mL. This study provided a new extraction technology for polysaccharides from Lycium barbarum.