Background: Hydrocephalus is a condition in which there is an abnormal build-up of CEREBROSPINAL FLUID within the ventricles and/or subarachnoid space, which leads to elevated intracranial pressure (ICP). (CSF) contains growth factors and cytokines secreted from the choroids plexus as well as subcommissural organs which are known as modulators of neurogenesis, differentiation and brain extracellular microenvironment and also show changes associated with neurological disorders and abnormalities of development. VEGF is the prime hypoxia inducible angiogenic factor. We assumed that increased ICP leads to reduced oxygen tension in brain tissue, which triggers VEGF gene transcription.Material and Method: Measurements were performed on (CSF) and serum aliquots obtained from control (n=16) and hydrocephalic patients (n=14), age- and sex-matched, were collected by lumbar puncture (LP) in the children hospital medical center of Tehran from 2006 to 2008. VEGF and total protein concentrations were determined by enzyme-linked immunosorbent assays (ELISA) and Bradford method, respectively.Results: VEGF and total protein concentrations were significantly elevated in hydrocephalus (CSF) samples compared with those in controls (p<0.05, p<0.001, respectively). There was only a slight insignificant elevation in serum VEGF concentrations.Conclusion: Under normal conditions there is only diffuse expression of VEGF in the brain, with the exception of some specialized cells of the choroid plexus. In contrast, under local or systemic hypoxia, neurons, astrocytes, and microglial cells all show enhanced VEGF expression. The present study shows that VEGF concentrations are much higher in the (CSF) of children with hydrocephalus than in control samples and VEGF may be involved in hydrocephalus pathophysiology.