Abstract: OBJECTIVE To evaluate the skin of mice comprehensively and study the effect of intervention with tremella polysaccharides by establishing mice model with outer-dry skin. METHODS Ten KM mice were placed in an artificial climate chamber to establish the model mice with outer-dry skin according to the "temperature-humidity-wind" comprehensive conditions; while other 90 KM mice, except the blank group, were kept under the conditions of external dryness. The intervention study of tremella polysaccharides was divided into oral and topical administration, mice of oral administration were randomly divided into blank control group and model control group (equal saline), tremella polysaccharide groups (400, 200, 100 mg·kg^-1 tremella polysaccharide); mice of topical administration were randomly divided into percutaneous blank group and model group (equal physiological saline), tremella polysaccharide group (tremella polysaccharide 10 mg·cm^-2) and positive control group (HA 10 mg·cm^-2), each group was treated by different ways of administration once a day for 20 days. The surface characteristics, water content, tissue structure, HA and AQP3 expression of mice were counted as obervation indicators of the skin situation under the intervention of Tremella polysaccharides with different administration methods. RESULTS After comprehensive evaluation of skin, the model was established successfully. Under the intervention of Tremella polysaccharides, compared with the blank group, the skin water content, HA and AQP3 content of the model group with oral and topical administration was decreased (P<0.05). Compared with the model group, the water content, HA content and AQP3 expression were significantly increased in each drug group (P<0.05), and the effect of 400 mg·kg^-1 tremella polysaccharide group was the best among oral groups and the topical tremella polysaccharide group was better than that of the positive control group among the external administration groups (P<0.05). Compared with the model group, the skin of each drug group, without obvious dandruff and crack, became sleeker and glossier; the hair of mice grew normally, the skin structure was intact, and the number of hair follicles and sebaceous glands increase. CONCLUSION Based on the theory of external dryness resulting in skin dryness, tremella polysaccharides can alleviate dryness of skin effectively that may related to the regulation of HA and AQP3 in the skin