Objective To investigate the effects of estrogen on the cognitive function and on the hippocampus neurons of SAMP8 mouse. Methods Forty five 6-month-old female SAMP8 were divided into three different groups: sham group, OVX group, OVX+E group, and SAMR1 mice were used as comparision of homologization. Morris water maze test was used to test the ability of learning and memory. HE staining and immunohistochemistry technique were used to reveal the neurons and neuronal nitric oxide synthase(nNOS) positive neurons in the CA1 subregion. Flow cytometry was used to detect the quantities of the nNOS in the hippocampus. Results The escape latency of the OVX group was that of the sham group（EM>P/EM><0.05）and the total number of crossing the platform of the OVX group was fewer than that of the sham group（EM>P/EM><0.05）. Estrogen replacement therapy could improve the learning and memory ability（EM>P/EM>>0.05）; The OVX group of the CA1 was significantly changed, and the nNOS positive neurons, average absorbance and the nNOS fluorescence index (FI) of the OVX group of the CA1 were shorter than that of the sham group（EM>P/EM><0.05）. The OVX+E group and the sham group showed no difference in results（EM>P/EM>>0.05）. Conclusion The present study suggests that estrogen can improve the ability of learning and memory, protect