Background: Glioblastoma Multiforme (GBM) is a grade IV glial brain tumor that is characterized by poorly differentiated anaplastic cells surrounding focal areas of necrosis and neovascularity. Objective: To identify role of Magnetic Resonance Imaging (MRI) in assessment of glioblastoma response to treatment Methods: This a prospective cohort study included 12 patients (4 males and 8 females) their ages ranged from 25 years to 69 (53.6 ± 15.1 years). patients with pathologically proved GBM grade IV (GBM) who were operated and received both radiotherapy and chemotherapy were enrolled to this study. MRI was done within 48 hours and 3 months postoperative. Imaging modalities applied in both MRI exams were: Conventional Magnetic Resonance imaging, MRI Diffusion weighted images, and Contrast imaging. Results: There was statistically significant reduction in edema, mass effect, T2 and FLAIR signals 3 months postoperatively in comparison to 48 hours MRI findings. Post-operative hemorrhagic signal reduced in follow up after 3 months but with no significant difference. Marginal enhancement in the immediate post-operative were detected in all cases, however, in the 3 months follow up was limited to 10 cases only with 8 of them also showed recurrent solid measurable component, DWI marginal restriction was the finding in the immediate 48h in 8 cases mostly related to surgical interference ischemia, however in the 3months follow up 6 of the measurable enhanced lesions displayed diffusion restriction and two of the measurable recurrent masses had not definite restriction. Conclusion: Immediate post operative MRI is a gold base line to discriminate the post operative sequel and recognize the different surgery related finding and for proper interpretation of therapy related response in the subsequent follow up imaging which intern could avoid unnecessary biopsies in follow up.