To investigate the molecular regulatory mechanism of integrity of blood-brain barrier (BBB) and learning and memory ability in Alzheimer's disease (AD) via PDGFR-β/TGF-β/Smad2/3 signaling pathway. Methods: Using the APP/PS1 transgenic mouse model of AD, the learning and memory abilities of mice were analyzed through water maze test and food search test. The proliferation rate and pericyte coverage rate in hippocampus were measured. The level of TGF-β R1 and its downstream signal pathway molecules, and the levels of tight junctions (TJs) were analyzed. After intraventricular microinjection with exogenous PDGF-BB and/or intraperitoneal injection with SB431542, the transgenic mice were analyzed by the above methods. After PDGF-BB and/or SB431542 treatment, permeability and transcellular resistance were tested in the BBB model in vitro. Results: Compared with the control group, APP/PS1 mice showed the learning and memory disability in the water maze test and food search test, the less proportion of desmin/lectin positive cells in the hippocampus, the lower levels of TGF-β R1, p-Smad2 and p-Smad3 protein, and the lower levels of TJs. Furthermore, exogenous PDGF-BB could significantly enhance the learning and memory ability, increase the pericyte coverage rate, raise the expression levels of TGF-β R1, p-Smad2 and p-Smad3 protein, and heighten the expression levels of TJs proteins. In contrast, SB431542 could partially inhibit the above effects of PDGF-BB treatment. In vitro tests showed that exogenous PDGF-BB could significantly reduce the final permeability coefficient of AD model group and increase the relative TEER value at 24 h; SB431542 can partially inhibit the above effects. Conclusion: PDGFR-β/TGF-β/Smad2/3 signal pathway may play a vital role in regulating the integrity of blood-brain barrier and the recovery of learning and memory ability in AD.