Tenuigenin (TEN), a major active component of the Chinese herb Polygala tenuifolia root, has been used to improve memory and cognitive function in Traditional Chinese Medicine for centuries.The present study was designed to explore the possible neuroprotective effect of TEN on the streptozotocin (STZ)-induced rat model of sporadic Alzheimer's disease (sAD).STZ was injected twice intracerebroventrically (3 mg/kg, ICV) on alternate days (day 1 and day 3) in Rats. Daily treatment with TEN (2, 4, and 8 mg/kg) starting from the first dose of STZ for 28 days. Memory-related behaviors were evaluated using the Morris water maze test. Hyperphosphorylation of tau proteins in hippocampus were measured by western blot assay. Superoxide dismutase activities, malondialdehyde, glutathione peroxidase and 4-hydroxy-2-nonenal adducts contents were also measured in the hippocampus.Treatment with TEN significantly improved STZ-induced cognitive damage, markedly reduced changes in malondialdehyde and 4-hydroxy-2-nonenal adducts, and significantly inhibited STZ-induced reduction in superoxide dismutase and glutathione peroxidase activities in the hippocampus. In addition, TEN decreased hyperphosphorylation of tau resulting from intracerebroventricular STZ (ICV-STZ) injection, and Nissl staining results showed that TEN has protective effects on hippocampal neurons.These results provide experimental evidence demonstrating preventive effect of TEN on cognitive dysfunction, oxidative stress, and hyperphosphorylation of tau in ICV-STZ rats. This study indicates that TEN may have beneficial effects in the treatment of neurodegenerative disorders such as AD.