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Objective: To study the mechanism of vasculogenic mimicry (VM) and its relation with chemotherapy in non-small cell lung cancer (NSCLC). Methods: 42 patients with NSCLC were collected, 19 belonged to the early stage (stage I+II) while 23 were late stage (stage III+IV). Moreover, 20 patients got surgical treatment and 22 got chemotherapy. We studied the relationship of VM with stage, chemotherapeutic effect, HIF-1α, MVD and clinicopathologic features. Results: VM in patients of early stages were significantly more than late stages (68.4% VS 26.1%, P=0.006), but no significant difference was found between effective and noneffective chemotherapy group (14.3% VS 26.7%, P=1.00). Furthermore, the positive rate of VM was proportional to HIF-1α (p=0.034). VM also showed a negative correlation with distant metastases and positive correlation with lymph nodes metastases (P< 0.05) while no correlation was found between VM and other clinicopathologic including sex, age, pathological pattern, tumor size and differentiation (P > 0.05). Conclusion: VM was generated during the early stage in NSCLC and correlated with lymph nodes metastases. As the disease progressed, VM may be replaced by vascular endothelial cells. No evidence has been found to demonstrate the correlation between VM and chemosensitivity. However, HIF-1α may make a difference in VM formation. Thus VM might be a novel therapeutic target, and used for clinical staging and treatment. [ABSTRACT FROM AUTHOR]