The effectiveness of radiotherapy and chemotherapy in high grade gliomas (HGG) depends on tumor micro-environment. We summarize our experience of the influence of spinal cord stimulation (SCS) on this micro-environment. Patients with HGG (n = 26) were assessed pre- and post-SCS, using: (1) Doppler in middle cerebral arteries (MCA) and (2) in common carotid arteries (CCA); (3) tumor blood-flow using single photon emission computed tomography (SPECT); (4) tumor-pO(2) (mmHg) using polarographic probes (eight tumor areas from five patients); and (5) tumor glucose metabolism using (18)F-fluoro-2-deoxyglucose ((18)FDG) positron emission tomography ((18)FDG-PET). Pre-SCS: tumor blood-flow was lower (P < 0.001) than peri-tumor areas and healthy contra-lateral areas. Tumor-pO(2) was lower (P < 0.042) than healthy tissue. Tumor glucose metabolism was higher than peri-tumor areas (P = 0.017) and healthy contra-lateral areas (P = 0.048). Post-SCS: there were increases in: MCA blood-flow (P ≤ 0.002), CCA blood-flow (P ≤ 0.013), tumor blood-flow (P = 0.033), tumor glucose metabolism (P = 0.027) and tumor-pO(2) (P = 0.022). The percentage of hypoxic values decreased (P = 0.007). SCS can modify tumor micro-environment. The potential usefulness of SCS in improving the effectiveness of radio-chemotherapy in HGG needs to be evaluated.