To investigate the modulatory effects of evodiamine on hypoxia-inducible factor-1 alpha(HIF-1α)/vascular endothelial growth factor(VEGF) signaling pathway in Lewis tumor-bearing mouse model.Methods:The tumor-bearing mouse model was established by subcutaneous injection of Lewis lung cancer cells.Then，the mice were randomized into model，positive control(cisplatin)，low-dose evodiamine，and high-dose evodiamine groups and treated with corresponding agents for 14 days.The tumor size in each group was measured to calculate the tumor inhibition rate，which reflected the inhibitory effect of evodiamine on tumor growth.Furthermore，qPCR was employed to examine the mRNA levels of HIF-1α and VEGF in the tumor tissue，and immunohistochemical staining to determine the protein levels of HIF-1α，VEGF，and platelet/endothelial cell adhesion molecule-1(CD31) in the tumor tissue.The microvessel density(MVD) in the tumor tissue was calculated.Results:Evodiamine significantly decreased the tumor size in Lewis tumor-bearing mouse model.The tumor inhibitions rate in the positive control，low-dose evodiamine，and high-dose evodiamine groups were 53.13%，20.49%，and 38.54%，respectively.Evodiamine down-regulated the mRNA and protein levels of HIF-1α and VEGF and decreased the MVD in the tumor tissue(P<0.01).Conclusion:Evodiamine could inhibit angiogenesis by down-regulating the expression of HIF-1α and VEGF to hinder the growth of lung tumor in tumor-bearing mice.