Objective To investigate the protective effect of Astragalus-Lily Granules on intestinal mucosa and intestinal flora homeostasis in mice under high altitude hypoxia condition. Methods We put mice into high altitude hypoxia cabin to establish high altitude hypoxia model mice. Sixty Kunming mice were randomly divided into control group, model group, Astragalus-Lily particles (ALP) low, medium and high dose groups [1.75, 3.5, 7g/(kg•d)] respectively. After three days of routine feeding, the ALP mice received drug by intragastric administration, once a day for continuous 17 days,control group and model group were given double distilled water in same volume. From the 15th day, all the mice but control group were exposed to simulated high altitude hypoxia condition for 3 days in a high altitude hypoxia cabin after they were gavaged for half an hour daily. By the 18th day, the fresh mouse feces were collected and smeared to observe the changes of microflora. The pathological changes of intestinal tissues were observed by HE staining and the expression of HIF-1αprotein in intestines was detected by immunohistochemistry. Results The enterococci and gram negative bacteria showed a higher proportion (65.2%±2.4% and 56.7%±3.3%, respectively) in the model group compared with the control group (24.7%±1.2%, 23.2%±1.5%, respectively, P