Neuregulin-1β (NRG-1β) is a growth factor with potent neuroprotective capacity. Growth-associated protein 43 (GAP-43) is expressed in dorsal root ganglion (DRG) neurons and an indicator of neuronal survival in vitro. The purpose of present study is to evaluate the effects of NRG-1β on GAP-43 expression in DRG neurons with excitotoxicity induced by glutamate (Glu) in vitro. The phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated protein kinase 1/2 (ERK1/2) signaling pathways involved in these effects were also determined. Embryonic rat DRG neurons were treated with Glu in the absence or presence of NRG-1β and PI3K inhibitor LY294002 and/or ERK1/2 inhibitor PD98059. After that, GAP-43 mRNA and GAP-43 protein levels were analyzed by real time-PCR and western blot assay, respectively. GAP-43 expression in situ was determined by immunofluorescent labeling. The results showed that the decreased GAP-43 levels induced by Glu could be partially reversed by the presence of NRG-1β. Inhibitors (LY294002, PD98059) either alone or in combination blocked the effects of NRG-1β. These data provide new insights of the actions of NRG-1β in sensory neurons.