In order to evaluate whether APP-Ab injection to hippocampus influence Morris water maze behavior and neuronal degeneration and to further investigate the potential mechanisms, rats were anaesthetized and fixed on a stereotaxic instrument and bilateral injection 1 μl of anti-APP antibody (10 g/L) was made using microsyringe. Meanwhile, NS or IgG-intrahippocampal-injected (1 μl; 10 g/L) rats served as vehicle controls. Antibodies were injected into the hippocampus (AP: -3.0; L and R: 2.0; V: 3.5 mm). The Morris water maze test was performed to test animals' learning and memory ability. After APP-Ab injection, cresyl violet and Fluoro-Jade B staining were used to investigate neuronal degeneration. Immunohistochemistry staining was used to detect MAP-2 and phosphorylated paxillin and tau distribution at hippocampus. APP-Ab injection to hippocampus could prolong the escape latency to find hidden platform and decreased the exploratory time and crossing numbers in the training quadrant. APP-Ab injection was also shown to cause neuronal cell death and degeneration by cresyl violet (CV) staining and Fluoro Jade-B (FJB) staining. Moreover, decreased MAP2 immunoreactivity, increased phosphorylated paxillin and phosphorylated tau immunostaining were observed in the pyramidal cells. It can be concluded that intrahippocampus injection of APP-Ab could induce cognitive deficits and neurodegenerative changes. APP-Ab injection also affected the distribution of MAP2, paxillin and tau protein.