Objective To observe changes of spacial learning and memory and the ultrastructure of hippocampus in perimenopausal depression model rats. Methods Thirty-six female SD rats were randomly divided into four groups(9 in each). Normal group wasn't given any stress, and stressed group was given isolation-housing in combination with chronic unexpected mild stress (CUMS) for 21 days. Ovariectomized group was given ovary resecting, and model group was made by resecting the ovaries of female rats, then giving isolation-housing in combination with 21 days of CUMS. Morris water maze test were used to test rats' behaviors. Light microscope and transmission electron microscope were used to observe the tissular structure of hippocampus. Results After ovaries resecting and 21 days of CUMS,the escape periods of rats in model group during the first three days ( (44.08 ± 18.29)s; ( 38.80 ± 19.07 ) s; ( 22.74 ± 14.13 ) s) were longer than ovariectomizd group ( (43.68 ± 10. 37 ) s; ( 20.28 ±17.75)s;(21.22 ± 11.91 )s] and normal group( (34.50 ± 11.08)s;(21.42 ± 14.32) s;( 13.94 ±9.76) s). HE staining showed that hippocampal pyramidal cell layer became thinner in rat model of depression,the gap between cells increased,and the cells arrayed in disorder,or loosely,even a large number of cells were lost. Transmission electron microscope showed that in rats of model group, hippocampal neurons were less, nuclear collapsed, the whole nuclear membrane was fuzzy and there were some local fractures in the nuclear membrane. Mitochondria within the cytoplasm were swelling and their ridges disappeared. Conclusion The decline of spacial learning and memory abilities in perimenopausal depression model rats might result from pathological changes in hippocampus.