Objective: Gliomas are the most common brain tumor in adults. Tumor-related endothelial cells are of neoplastic nature and have malignantproperties such as proliferation and invasion. Therefore, antiangiogenic approaches have several advantages compared with conventional chemotherapeutic approaches. The target of antiangiogenic treatment is to ensure a decrease in systemic side effects because there are endothelial cells and other supportive cells belonging to the vessel walls. The purpose of this study was to increase the oxygenation of the environment with hyperbaric oxygen therapy (HBOT) and to prevent the angiogenic effect of hypoxia-related factors. We also tried to prevent angiogenesis by using sorafenib (SOR), which is a chemotherapeutic agent that blocks the receptors of these factors. Also, this study compared the effect of these both and to put into for their effect. In this regard, parameters such as the tumor size, vascularization rate, midkine (MK), apoptosis- and angiogenesis-related transcription tumor necrosis factor (TNF) alfa, and IL6 were compared in the relevant groups.