Abstract: Objective: To investigate the protective and delayed effects of Gastrodia elata polysaccharide on non-alcoholic fatty liver (NAFLD) and its molecular mechanism. Methods:60 ICR mice were randomly divided into normal group, model group and Gastrodia elata polysaccharide group (50, 100 and 200 mg/kg). Except the normal group, the other groups were given high-fat diet to induce NAFLD model. At the same time, the corresponding drugs were given once a day for 10 weeks. At 30 min after the last administration, the body weight and organ index of mice were recorded, the pathological changes of liver tissue were evaluated by histopathology. At the same time, the activity of serum aspartate amino transferase (AST) and alanine amino transferase (ALT) were measured, and the related signal transduction pathways were examined including oxidative stress injury and lipid metabolism. Results:Compared with the model group, the activity of AST and ALT in serum were significantly decreased (P<0.05), and the pathological symptoms of fatty liver tissue was alleviated, and the level of genes expression related to lipid accumulation were regulated to improve lipid metabolism (P<0.05); In addition, Gastrodia elata polysaccharide also improved oxidative stress injury by upregulating Nrf2/GPX signaling pathway (P<0.05), inhibited the expression of NF-κB, TNF-α, IL-1β, iNOS and COX-2 proteins related to inflammatory response (P<0.05), and inhibited the expression of Bax and upregulated Bcl-2 proteins (P<0.05). Conclusion: Gastrodia elata Blume polysaccharide (GBP) can improve the liver function of NAFLD model mice, regulate the level of lipid metabolism and reduce the accumulation of fat, alleviate the oxidative stress injury of liver and inhibit inflammation to protect and delay NAFLD symptoms caused by high fat diet.