Abstract: Objective Recently reasearch suggests that Nogo A expressed by oligodendrocytes and its receptor NgR may be involved in the etiology of neurophology of PKU or Hyperphenylalaninemia as an inhibitors, yet the action of Nogo A expressed by neuron is still not known. And whether its the specific antagonist to NgR (NEP1-40) can affect its expression. So the study was designed to investigate the effect by NEP1-40 on Nogo A in high phenyalanine(Phe) in vitro. Methods Cells was dissected from the cerebral cortex of E16~E18 embryos of SD rat， Real-time PCR and Western-Blot were used to evaluate the mRNA and protein of Nogo A respectively. The growth cones, axon and the Nogo A location were performed by immunofluorescence and immunohistochemistry respectively. Results Compared to the control, The mRNA and protein level of Nogo A with Phe for 12h, 24h and 48h were slightly reduced. NEP1-40 can upregulate expression of Nogo A on neuron in the high Phe condition with high level, but has no act on normal neuron. Conclusion NEP1-40 can promote expression of Nogo A on neuron in high Phe, which can help the neuron grow.