【 Abstract】 Objective To investigate the effect of 5-Aza-CdR on Notch1 pathway and neural regeneration, and to explore the effects of 5-Aza-CdR on learning memory ability in mice by exploring active avoidance behavioral experiments on mice. Methods Sixty 6- to 8-week-old ICR male SPF-grade mice were divided into two groups, and 5-Aza-CdR was administered to one group of mice via lateral ventricular injection (i.c.v.), while the other group was injected with BSA as a control group. 5-Aza-CdR was administered to mice by lateral ventricular injection (i.c.v). mRNA and protein expression levels of Notch1 and HES1 were detected by real-time PCR and Western blot 24 hours after injection; 5-bromo-2'-deoxyuridine (BrdU)-positive cells were observed by laser confocal microscopy and Notch1 expression in hippocampal DG by laser confocal microscopy; Notch1 methylation changes were detected by MS-PCR; and learning and memory behaviours of mice were assessed by measuring passive avoidance tests and shuttle avoidance assays. RESULTS Injection of 5-Aza-CdR increased hippocampal Notch1 pathway activity and promoted neuronal regeneration in the DG region, decreased methylation levels in the Notch1 promoter region, and enhanced the ability of mice to perform active avoidance behaviour. Conclusion The effect of 5-Aza-CdR on active avoidance behavior may be related to the influence of hippocampal neural regeneration through the Notch1 pathway.