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Background:Gastrointestinal dysmotility is commonly seen in individuals exposed to acute plateau hypoxia. Its pathogenic mechanism is still not clear and intervention study is rarely performed. Aims:To investigate the influence of plateau hypoxia on small intestinal motility of rats,its possible mechanism,and the intervention effect of raw Atractylodes macrocephala. Methods:Seventy Wistar rats were randomly divided into 7 groups:control group,two high altitude model groups(3 500 m and 5 000 m),trimebutine and raw Atractylodes macrocephala groups at 3 500 m or 5 000 m altitude. Rats in six experiment groups were placed in a hypobaric chamber mimicking 3 500 m or 5 000 m altitude and given trimebutine/ raw Atractylodes macrocephala/ saline intragastrically for 3 days. Then all the rats were lavaged with 2 mL ink and sacrificed 30 minutes later. The propulsion rate of ink in small intestine was measured,the pathological changes of small intestine tissue were examined,and the expression of 5-HT4 receptor was determined by immunohistochemistry. Results:Compared with control group,the propulsion rate of small intestine and immunopositive area of 5-HT4 receptor were reduced in model group at 3 500 m altitude,while those in model group at 5 000 m altitude were increased(P ﹤0. 05). Moderate-to-severe mucosal injury was observed in two model groups. In model rats treated with raw Atractylodes macrocephala,the abnormalities in small intestine propulsion and 5-HT4 receptor induced by high altitude(3 500 m and 5 000 m)returned to the control level(P ﹤ 0. 05),and the mucosal injury ameliorated simultaneously. Efficacy of raw Atractylodes macrocephala was prior to trimebutine,a positive control. Conclusions:Acute plateau hypoxia may induce small intestine dysmotility with diverse manifestations,and altitude is a crucial determinant in this process. Raw Atractylodes macrocephala can exert therapeutic effect on this dysmotility by modulating 5-HT4 receptor,and it is also effective in repairing mucosal injury.