Objective To explore the effects of estrogen on learning and memory ability, and hippocampal p53 and superoxide dismutase(SOD) expression in rats with vascular dementia. Methods Sixty rats were randomly divided into four groups,and given estrogen or normal saline for 8 weeks.Morris water maze test was used to measure the learning and memory ability,and the expression of p53 protein and SOD activities were examined in the hippocampus. Results As compared with the low dose estrogen group, the escape latency of rats, the Quadrant III activity time and the number of cross platform were significantly shortened in the high dose estrogen group at the first day(P<0. 05).The expression of hippocampal p53 (0. 25±0. 01)in the low dose estrogen group was significantly lower than that in high dose estrogen group (0. 30±0. 02). Conclusion Estrogen decreases the expression of p53 protein and enhance the activity of SOD.It can protect the hippocampus related to the memory ability. Key words: Estrogen; Vascular dementia; Hippocampus; p53; Superoxide dismutase