OBJECTIVE: To investigate the improvement effects and its mechanism of grape seed proanthoeyanidins (GSP) on learning and memory ability of Alzheimer’s disease (AD) model rats. METHODS: Totally 50 rats were randomly divided into sham operation group, model group and GSP high-dose, medium-dose and low-dose groups (400, 200, 100 mg/kg). Those groups were given Aβ1-42 in hippocampus of rats to establish AD model except sham operation group and given relevant medicine intragastrically 48 h after modeling. Sham operation group and model group were given constant volume of normal saline intragastrically, once a day, for consecutive 21 d. 14 d after administration, new object recognition test was adopted to test new recognition index (TI). Morris water maze test was conducted since 16 d after administration. The escape incubation period of rats were recorded 5 d during learning. Exploration incubation period and the times of exploration were recorded after last administration. Western blot was used to detect the expression of NLRP3 in rat hippocampus. ELISA was used to determine the content of IL-6 and IL-1β in rat hippocampus. RESULTS: There was no statistical significance in escape incubation period among 5 groups within 5 d of Morris water maze learning (P>0.05). Compared with sham operation group, TI of model group was decreased significantly, while exploration incubation period was prolonged significantly; the times of exploration was decreased significantly; the levels of NLRP3, IL-6 and IL-1β in hippocampus were increased significantly, with statistical significance (P<0.05). Compared with model group, exploration incubation period of GSP groups were shortened significantly, while the times of exploration and TI were increased significantly; the levels of NLRP3, IL-6 and IL-1β in hippocampus were decreased significantly, with statistical significance (P<0.05). CONCLUSIONS: GSP can improve the memory ability of AD model rats, the mechanism of which may be associated with inhibiting NLRP3 inflammatory corpuscle pathway and reducing the generation of inflammatory factors as IL-6 and IL-1β.