Abstract: To study the related changes of nitric oxide synthase (nNOS) positive neurons in the sections of the hippocampus of female rabbit (SpragueDawley strain) after ovariectomy and estrogen replacement therapy, the distribution and structure of nNOS positive neurons was observed in rabbit hippocampus using SABC immunohistochemical technique, which provides basic theories for preventing and treating Alzheimer′s disease with estrogen replacement therapy. The results showed: There are comprehensive nNOSpositive staining cells in all regions of hippocampus. After ovariectomy, the changes of nNOS positive neurons in subregion of hippocampus were not equal: the number of positive neurons in subiculum CA1, CA3 and dentate gyrus(DG) were decreased compared with control group (P<0.05), while the number of positive neurons in subiculum CA2 was increased (P<0.05). The average section area of positive neuron was smaller and the length of the longest process become shorter and the number of first tuber turns were less in subiculum CA1, CA3 and DG than that in control group(P<0.05). The average section area of positive neuron was smaller while the length of the longest process and the number of first tuber have no remarkable change in CA2 than that in control group (P>0.05). Four kinds index of positive cells in the subregion of hippocampus showed no significant difference between estradiolreplacement therapy and the control group(P>0.05).The results indicated that estrogen maybe affect the learning and memory by influencing the expression of nNOS in hippocampus.