Glioblastoma (GBM) induces both vasogenic edema and extensive tumor cells infiltration, both of which present with similar appearance and not be differentiated on conventional MRI. To distinguish between these infiltrative tumor and vasogenic edema components within the nonenhancing lesion area using novel techniques thus holds great clinical importance. Oxygen-enhanced MRI may directly reflect tissue oxygenation, has shown promising applications in the measurement of hypoxia or radiation-induced necrosis. Therefore, in this study we explored the possibility to differentiate vasogenic edema from infiltrative tumor in patients with GBM using oxygen-enhanced MRI. The results showed significant more negative ΔR1 levels (p < 0.05) were observed in the infiltrative tumor area compared to those in the vasogenic edema and tumor site. Oxygen-enhanced MR imaging has thus the potential to differentiate infiltrative tumor from vasogenic edema in glioblastoma.