Abstract: Objective To explore the influence of hyperhomocysteinemia(HHcy)on learning and memory ability and expression of β-amyloid precursor protein of hippocampus and the intervention effect of folic acid(FA)in rats. Methods Forty Wistar rats were randomly divided into normal control group,HHcy group,and two FA intervention groups(low and high dose).Methionine(1 g/kg·d)was dissolved in drinking water to make HHcy model.Treatment with FA(0.7 and 3.4 mg/kg·d)via intragastric intubation was administered in FA groups for 8 weeks.Plasma concentrations of homocysteinemia(Hcy)and FA before and after the experiment were measured.The rats'learning and memory abilities were tested by Morris water maze test.At the end of 8 weeks experiment,immunohistochemistry was used to observe the expression of β-arnyloid precusor protein(APP)in hippocampus. Results Compared with the normal control and FA groups,the escape latency in HHcy group was significantly longer;the numbers of passing the platform region was significantly less;the staying time in the platform region was significantly shorter(P<0.05-0.01);and the mean values of APP and its metabolic secretase in region of hippocampus was significantly higher(P<0.01).The results of all tests were not significantly different between the normal control group and FA groups. Conclusion HHcy can induce learning and memory impairment and decreased the expression of APP in hippocampus in rats.FA supplementation could attenuate the adverse effects.