This study examined the protective effects of Ginkgo biloba extract (GbE) on the learning and memory function in aluminum-treated rats and potential mechanisms. Wistar rats were given daily aluminum chloride 500 mg/kg, i.g, for one month, followed by continuous exposure via the drinking water containing 1600 ppm aluminum chloride for up to 5 months. The ability of spatial learning and memory was tested by Morris water maze. Aluminum administration significantly increased escape latency and searching distance, indicative of brain dysfunction. GbE treatment (50-200 mg/kg, i.g) significantly protected against aluminum-induced brain dysfunction, as evidenced by decreased escape latency and searching distance compared with the Al alone group. To examine the mechanisms of the protection, the expressions of amyloid precursor protein (APP) and caspase-3 in brain regions were examined by immunohistochemistry. GbE treatment reduced the contents of APP and caspase-3 in hippocampus of aluminum-treated rats in a dose-dependent manner. At the highest dose of GbE (200 mg/kg), the immunostain for APP and caspase-3 was returned to normal levels. In summary, this study demonstrates that GbE is effective in improving the ability of spatial learning and memory of aluminum-intoxicated rats. This protection appears to be due to a decreased expression of APP and caspase-3 in rat brain, resulting in a decrease in the production of insoluble fragments of Abeta-amyloid.