To identify a novel treatment modality for postoperative, glioma-related refractory cerebral edema (RCE), eight patients with postoperative RCE received chemotherapy between January 2008 and July 2012 were enrolled. There were five males and three females aged between 24 and 65 years (mean 45.7 years). Vascular endothelial growth factor (VEGF) levels in the cerebrospinal fluid were measured by enzyme-linked immunosorbent assay pre- and postchemotherapy. After 3 days postchemotherapy, midline shift improved from 13.14 +/- 0.65 to 7.21 +/- 0.55 mm and compressed or effaced basilar cisterns disappeared based on cranial computed tomographic scans. Glascow Coma Scale scores in patients significantly improved from 11.13 +/- 0.52 to 14.50 +/- 0.27 after chemotherapy. Two patients developed grade 1 leukopenia after 3 weeks, and one patient had grade 1 thrombocytopenia 2 weeks after chemotherapy. No fatal complications occurred. The edematous volume reduced from 77,074 +/- 6,813 to 27,874 +/- 5,073 mm(3) (p < 0.001). VEGF levels were significantly downregulated after chemotherapy (from 543.8 +/- 76.39 to 122.2 +/- 59.30 pg/ml, p < 0.001). Chemotherapy may serve to alleviate glioma-related RCE by reducing VEGF levels, especially in patients who were insensitive to decompressive craniectomy.