Purpose This study aims to examine the effect of a novel recombinant human endostatin (rh-Endo)on tumor vasculature in both animal models and cancer patients, and to explore and evaluate the optimal scheduling of rh-Endo and radiotherapy (RT).Experimental Design Tumor-perfusion parameters and hypoxia were monitored after rh-Endo treatment in 10 non-small cell lung-cancer patients.Eight-week female C57BL/6J mice were randomized to receive rh-Endo or a control(saline) once daily for 12 days when the LLC tumor reached approximately 100~150 mm3.On planned days, tumors were measured for the apoptosis of tumor cells, microvessel density, pericytes,blood-vessel morphology, and tumor hypoxia.The tumor response under different combinations of schedules of rh-Endo and RT was also evaluated.Results Tumor hypoxia was significantly reduced five days after rh-Endo in non-small cell lung-cancer patients.Similar results were shown in the Lewis lung-carcinoma mice model, in which hypoxia was also improved five days after rh-Endo treatment.The anti-tumor effect was markedly enhanced when RT was administered within the remodeling period compared with any other treatment schedule.In addition, rh-Endo treatment remodeled the tumor vasculature after five days, primarily by reducing microvessel density and increasing the pericytic coverage of the vessel endothelium.Conclusion This study suggests a similar hypoxic improvement in animals and patients by rh-Endo treatment, which also enhances the radioresponse within the vasculature-remodeling period.The optimal clinical combination of rh-Endo and RT warrants further investigation.