〔Abstract〕 Objective To explore the effects of neurotropin(NTP) on Notch signaling pathway and hippocampus neurons autophagy in Alzheimer′s disease(AD) model rats. Methods 45 SD rats were randomly divided into control group, model group and NTP group equally. Model group and NTP group were intraperitoneally injected with D-galactose(100 mg/kg) and hippocampus injected with Aβ1-42(5 μl) to establish AD rat models. NTP group was intraperitoneally injected with NTP(1.2 Nu/kg) for 2 weeks intervention. The learning and memory ability of rats in each group was detected by Morris water maze. The pathological changes of hippocampus tissues were observed by HE staining. The apoptosis of hippocampus neurons was detected by TUNEL method. The autophagy of hippocampus neurons was observed by electron microscope. Western blot was performed to detect Notch signaling pathway and the expressions of Caspase-3, Bcl-2, Bax, Beclin1 and LC3-Ⅱ/LC3-Ⅰ. Results Compared with the control group, the learning and memory ability of the model group and NTP group significantly decreased(P<0.05), while apoptosis rate of hippocampus tissue cells significantly increased(P<0.05). The expressions of Bcl-2, Beclin-1, Notch1, NICD and Hes5 proteins were significantly down-regulated, while the expressions of Caspase-3 and Bax were significantly up-regulated(P<0.05). Compared with the model group, learning and memory ability of the NTP group significantly increased(P<0.05), the expressions of Bcl-2, Beclin-1, LC3-Ⅱ/LC3-Ⅰ, Notch1, NICD and Hes5 in hippocampus tissues were significantly up-regulated(P<0.05), while the expressions of Caspase-3 and Bax protein were significantly down-regulated(P<0.05). HE staining showed that pathological changes in hippocampus tissues of rats in the NTP group were significantly reduced. Conclusion NTP can induce hippocampus neurons autophagy, improve learning and memory ability of AD rats and protect brain tissue damage by regulating Notch signaling pathway.