Abstract: In this study, Ganoderma lingzhi mycelium powder was used as material to extract polysaccharides from Ganoderma lingzhi mycelium by water extraction and alcohol deposition method. On the basis of single factor experiment, response surface methodology was combined to optimize the extraction process of polysaccharides from Ganoderma lingzhi mycelium. Proteins and small molecules were removed by Sevage method and dialysis method, then, the preliminary purification of Ganoderma lingzhi mycelium polysaccharide (SGP) was obtained. Animal model: 60 mice were randomly divided into blank control group, model group, positive control group and low, medium and high administration groups (125, 250 and 500 mg/kg·bw). Except for blank group, each group was given 56° Beijing Red Star Erguotou by gavage at a dose of 0.1 mL/10 g·bw to establish a chronic alcohol liver injury model. Starting from the 15th day, 4 h after modeling, each administration group was given intragastric administration of silybin (200 mg/kg·bw) and different doses of SGP solution, respectively, and dissected after 2 consecutive weeks. The levels of aspartate amino transferase (AST), aspartate transaminase (ALT), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), total cholesterol (TC), triglyceride (TG), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in serum and liver tissues of mice were determined by kit method, and the liver pathological sections of mice were observed. The results showed that the optimal extraction conditions of polysaccharides from Ganoderma lingzhi mycelium were 89 ℃, 2.5 h and liquid/solid ratio 85:1 mL/g. Under these conditions, the yield of polysaccharides was 3.44%. Animal experiment results showed that the liver index of mice in SGP medium and high dose groups was significantly decreased (P<0.01). The activities of CAT, SOD and GSH-PX in liver and serum of SGP medium and high dose groups were significantly increased (P<0.05), the activities of ALT and AST and the contents of MDA, TC, TG, IL-6, IL-1β and TNF-α were significantly decreased in SGP high-dose group (P<0.01). The results of pathological tissue sections showed that SGP could significantly improve liver damage. These results indicate that SGP can play a protective role in mice with chronic alcoholic liver injury by improving the oxidative stress level, lipid metabolism level and reducing the content of inflammatory factors in mouse liver cells.