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In present study we investigated whether periphery inflammatory pain can induce apoptosis of hippocampal neurons and investigated its profound mechanism Rats were subcutaneously injected with 0.2ml 5% formalin into the ventral surface of the right hind paw to induce periphery inflammatory pain.Flow cytometry was used to assay the ratio of apoptosis of hippocampal neurons,and the immunohistochemistry was used to observe the expression of proapoptotic p53 protein in hippocampal subregions.On the second day after the injection of formalin,the ratio of apoptosis of hippocampal neurons significantly increased compared with the control group.The increase in ratio of neuronal apoptosis peaked on the third day and decreased on the forth day.Meanwhile the periphery inflammatory pain resulted in an upregulation in expression of p53 protein in the CA1,CA3 and dentate gyms regions of the rat hippocampus.