Objective This study aimed to establish a reliable animal model of Alzheimer’ s disease (AD) with phlegm and stagnation to provide a corresponding animal model for the prevention and treatment of AD by Chinese medicine and to provide a reference on animal modelling method ology for the establishment of animal models combining disease and TCM evidence. Methods APP / PS1 2×Tg mice were used as AD model animals. The pathological state of “ stasis” was simulated by ice water bath and the pathological state of “ phlegm” was simulated by high-fat diet feeding. The two were combined to simulate the pathological state of “ phlegm and stasis interconnection”. The mice in different groups were treated differently: the AD-phlegm group was given a high-fat diet, the AD-stasis group was given an ice-water bath, the AD-phlegm-stasis group was given both a high-fat diet and an ice-water bath, and the AD-disease model group was left untreated. Non-transgenic C57BL/ 6J mice with the same genetic background were the control group. The differences in AD- like behavioral changes,objective changes in tongue image, blood rheology and lipid alterations and relevant protein content in hippocampal tissue were examined at 14 days after modeling. Results After 14 days of modeling, the AD-like behavioral changes and relevant protein content of mice in the AD groups were significantly changed compared with those in the control group. The tongue color was dark red in the AD-disease model group compared with result in the AD-model group; the hemorheology index of the AD-stasis group and the blood lipid index of the AD-phlegm group were increased. The related indexes of AD-phlegm-stasis interconnection group were significantly increased. Conclusions The combination of ice-water bath and high-fat diet to treat APP / PS1 mice for 14 days successfully established the combined animal model of AD-phlegm-stasis syndrome. This method has a high modeling rate, fits well with clinical symptoms and may represent a useful experimental animal system for subsequent studies.