Neuregulin-1 (NRG-1) is a member of the epidermal growth factor family. Our previous study showed that NRG-1 protected neurons from apoptosis following focal cerebral ischemia by the inhibition of caspase-3 and TNF-alpha expression However, the molecular signaling mechanisms for this action of NRG-1 following cerebral ischemia are not fully understood. Presently, activation of the PI3K/Akt pathway has been implicated as a major contributor to neuronal survival after an ischemic insult. In the present study, we investigated whether NRG-1 modulates the activation of Akt and its downstream targets Bad and Bcl-2 expression after transient focal cerebral ischemia by intralummal blockade of the middle cerebral artery. Western blot was employed to analyze the change of phosphorylated Akt (p-Akt) expression, reverse transcription and polymerization chain reaction (RT-PCR) were used to measure changes of Bcl-2 mRNA. The level of phosphorylation of Bad (p-Bad) was determined using an enzyme-linked immunosorbent assay (ELISA) Our results showed that recombinant human NRG-1(3 0 ng.kg(-1)) significantly increased the expression of p-Akt protein. Bcl-2 mRNA, and the level of p-Bad, respectively, whereas administration of LY294002, a specific inhibitor of PI3K. significantly decreased the expression of p-Akt, p-Bad, and Bcl-2 induced by NRG-1 after a 60 min ischemic insult, followed by 24 h of reperfusion These results Indicate that NRG-1 may be involved in regulating the expression of Bcl-2 and p-Bad through the PI3K/Akt pathway after transient focal cerebral ischernia