Baicalein may act on the benzodiazepine binding sites to exert an anxiolytic-like effect in mice. Since many benzodiazepine drugs have amnesic side-effect and baicalein can protect cultured cortical neurons from beta-amyloid peptide-(25-35)-induced toxicity, this study examined the amnesic effect of baicalein and its effects on beta-amyloid peptide-(25-35) (3 nmol/mouse, i.c.v.)-induced amnesia in mice. Using the step-through passive avoidance test, the results showed that baicalein (10-100 mg/kg, i.p.), unlike the benzodiazepine drug chlordiazepoxide (10 mg/kg, i.p.), had no significant amnesic effect. Baicalein (10-50 mg/kg, i.p.) also had no facilitating effect on the learning and memory. However, one dosage pretreatment, but not post-treatment, of baicalein (5 or 10 mg/kg, i.p.) attenuated beta-amyloid peptide-(25-35)-induced amnesia. Interestingly, post-treatment for 7 or 13 days of baicalein (10-15 mg/kg/day, i.p.), like melatonin (10 mg/kg/day, i.p.), also attenuated beta-amyloid peptide-(25-35)-induced amnesia. Therefore, this study demonstrated that baicalein has protective effect on beta-amyloid peptide-(25-35)-induced amnesia.