【Abstract】Objective To investigate the influences of longterm highdose glucocorticoids (GCs) on the digestive tract hypoxiainducible factor (HIF1α)/vascular endothelial growth factor (VEGF) pathway in asthmatic rats. Methods 60 SPF rats were selected, and 15 were randomly selected as normal control group, the rest rats were divided into model group, conventional dose dexamethasone group (DXMS group) and highdose dexamethasone group (DXMSH group). After 8 weeks of atomization treatment, HE staining was used to detect the pathological changes of lung tissues and gastric mucosa. The levels of serum gastrin (CAS), plasma Dlactic acid, diamine oxidase (DAO), motilin (MTL), and vasoactive intestinal peptide (VIP) were measured by ELISA. The plasma prostaglandin (6KetoPGF1α) level was measured by radioimmunoassay. RTqPCR was used to detect the expressions of HIF1α and VEGF mRNAs in gastric mucosa. Western blot was used to detect the expressions of HIF1α and VEGF proteins. Results HE staining showed that the inflammatory cell infiltration in the peribronchial and perivascular connective tissues of the model group was significantly higher than that of the normal control group (P＜005). Lymphocyte infiltration in group DXMS and group DXMSH was significantly lower than that in model group. Lymphocyte infiltration in group DXMSH was less than that in group DXMS. ELISA results showed that DAO, DLactate and VIP in DXMS group and DXMSH group were significantly higher than those in model group (P＜005). CAS and MTL were significantly lower than those in the model group (P＜005). DAO, DLactate and VIP in group DXMSH were significantly higher than those in DXMS group (P＜005). CAS and MTL were significantly lower than those in group DXMS (P＜005). HE staining of gastric mucosa showed there were no pathological changes such as edema, hyperemia, and inflammatory cell infiltration in normal control group and model group, edema and inflammatory cell infiltration were found in group DXMS, edema, mild bleeding, inflammation, and epithelial cell injury were found in group DXMSH. RTqPCR results showed that there was no significant change in HIF1α and VEGF mRNAs levels in normal control group and model group. HIF1α and VEGF mRNAs in group DXMS and group DXMSH were significantly higher than those in model group, HIF1α and VEGF mRNAs in group DXMSH were significantly higher than those in DXMS group. Western blot results showed that HIF1α and VEGF proteins in group DXMS and group DXMSH were significantly higher than those in model group. The HIF1α and VEGF proteins in group DXMSH were significantly higher than those in group DXMS. ConclusionLongterm highdose glucocorticoids may cause digestive tract injury in asthmatic rats through the HIF1α/VEGF pathway.