Objective To explore the expression of p53 protein and its relationship with the PI3K/Akt signal pathway in subarachnoid hemorrhage (SAH). Methods SAH was induced in mice by puncture of internal carotid artety. Seventy-two male mice were randomly divided into sham group, SAH group, LY (SAH+LY294002) group. The animals were sacrified at 0, the 3rd, the 6th, the 9th, the 12th and the 24th hour, to observe the expression of p53 and p-Akt in the brain with immunohistochemisty and Western blotting. The morphological changes of the neurons were studied by light microscope. RT-PCR was preformed for detecting the expression change of p53 and p-Akt mRNA. Results Neurons in the hippocampal CA1 region after SAH showed typical apoptotic features under light microscope. The expression of p53 and p-Akt protein was higher in SAH group than in sham group. Compared with SAH group, the expression of p-Akt decreased while the p53 was increased with the extension of time in LY group. Conclusion p53 and p-Akt are increased in cerebral cortex of mice after SAH. PI3K/Akt signal pathway could protect the brain neurons by modulating the p53 expression, which could induce the cell apoptosis.