Baicalein (Baic), is a natural flavonoid, which was isolated for the first time from the roots of the plant Scutellaria baicalensis, variety, Georgi. Numerous studies have shown that Baic has many pharmacological properties and a variety of important biological activities such as its anti-inflammatory, anticancer and neuroprotective activity. However, its effects on the neuropathology of Alzheimer's disease (AD) have not been well studied. Brain-derived neurotrophic factor (BDNF) is a neurotrophin with vital functions in the survival of neuronal cells. The cAMP response element binding protein (CREB) is an essential neuroprotein for long-term changes in synaptic plasticity that mediate the conversion of short-term memory to long-term memory. This study aimed to investigate the effects of Baic pretreatment on cognitive and cholinergic deficiency, oxidative and molecular status, and neural protection against neuroinflammation in the animal model of dementia represented by zebrafish (Danio rerio) which was induced by immersion administration of a muscarinic cholinergic receptor blocker represented by scopolamine (Sco 100 μM). Baic (1, 3 and 5 μg / L) was administered by immersion to zebrafish once a day for 16 days. To assess the level of anxiety of zebrafish we used the new aquarium diving test (NTT), to assess the spatial memory we used the Y maze test, and to assess the recognition memory we used the new object recognition test (NOR). To evaluate the effects of Baic on the oxidative and cholinergic status in the zebrafishes brain, we evaluated the specific activity of Superoxide dismutase (SOD), Catalase (CAT), Malondialdehyde (MDA) and Acetylcholinesterase (AChE) activity. Also, in this study we investigated the effects of Baic on bdnf and creb mRNA expression. Our results show that Baic can effectively restore the antioxidant defense mechanism by increasing the level of antioxidant activity in the brain. Baic also can improve cognitive dysfunction of amnesic fish by increasing the absolute gene expression of bdnf and creb and by inhibiting AChE, which is also correlated with improved memory parameters, as shown in behavioral approaches (NTT, Y maze and NOR). The authors state that they have no conflicts of interest.