Background and Objective: Vascular endothelial growth factor (VEGF) and its receptors (VEGF-R1 and R2) are major regulators of angiogenesis. This study was designed to assess serum levels of VEGF and VEGF-R1 and their prognostic significance in newly diagnosed childhood acute leukemia. Materials and Methods: For this purpose, VEGF and VEGF-R1 were determined using enzyme linked immuno-sorbant assay (ELISA) in samples obtained before treatment. Demographic data were recorded. Bone marrow blast percentage was counted on diagnosis and 2 weeks after induction therapy. A p value less than 0.05 considered significant. Results: Fifty-three children (22 boys and 31 girls) with newly diagnosed acute leukemia were enrolled in the study. Most cases (56.6%) were pre B cell ALL. Mean value of VEFG-A in good responders was 55.13 ± 24.96 pg/ml and in poor responders it was 94.46 ± 15.75 (p<0.0001). Mean valve of VEGF-R1 in good and poor responders was 0.132 ± 0.0653 and 0.1665 ± 0.0857 pg/ml respectively (p>0.05). Using ROC curve, we found out a cut-off point of 76 pg/ml to discriminate poor response to chemotherapy. Conclusion: Soluble VEGF-A is an independent factor for response to therapy in childhood leukemia and leukemic patients with sVEGF-A level over 76 pg/ml will have poor response to treatment.