Abstract: Objective: To isolate and purify the polysaccharides from Lycium barbarum and study its in vitro antioxidant activity and in vivo anti-aging effect. Methods: Crude polysaccharides from Lycium barbarum were obtained by water extraction and alcohol precipitation, and then LBP was isolated and purified from crude polysaccharides by Sevage reagent and DEAE-52 cellulose ion exchange resin. By measuring the scavenging ability of LBP to DPPH free radical, hydroxyl radical and ABTS⁺ free radical, and Fe³⁺ reduction, the antioxidant ability of LBP in vitro was evaluated. The aging mouse model was established by D-galactose. After administration, the body weights and organ indexes of mice in each group were compared. The levels of MDA, SOD, GSH-Px and CAT in serum, liver and brain were measured. The protein expression of Nrf-2 and HO-1 in liver tissue was detected by Western blotting. Results: The content of LBP after isolation and purification was 86.64%±2.34%. The IC₅₀ values of scavenging ability of LBP to DPPH free radical, hydroxyl radical and ABTS⁺ free radical were 0.2081±0.0182, 0.7132±0.0220 and 0.3646±0.0138 mg/mL, respectively. Compared with the model group, the body weights and organ indexes of the mice in positive and high dose of LBP groups were significantly increased (P<0.05 or P<0.01). The levels of SOD, CAT and GSH-Px in serum, liver and brain of mice in positive and high dose of LBP groups were significantly increased, and the level of MDA was significantly decreased (P<0.01). The expression level of Nrf-2 protein in liver tissue increased significantly except for in the low dose of LBP group (P<0.05), and the expression level of HO-1 protein increased significantly in all groups (P<0.05 or P<0.01). Conclusion: LBP from Lycium barbarum has strong antioxidant ability and certain anti-aging effect, and its mechanism may be related to Nrf-2/HO-1 signal pathway.