Objective(s):Alzheimer’s disease (AD), the most common cause of dementia, is one of the leading causes of morbidity and death in the world. Currently, treatment mostly used to slow down the disease progression. Herbal remedies are considered by many in the community as a natural and safe treatment with fewer side effects. Silibinin, the active ingredient ofSilybum marionum, has anti-oxidant, neurotrophic and neuroprotective characteristics. Therefore, here, the effect of different doses of Silibinin extract on oxidative stress and expression of neurotrophic factors was investigated.Materials and Methods:Forty eight male Wistar rats were randomly divided into sham, lesion; Aβ1-40injection, lesion-treatment; Aβ1-40injection followed by different doses of silibinin (50, 100, 200 mg / kg) through gavage and lesion-vehicle group; Aβ1-40injection + vehicle of silibinin. Morris water Maze (MWM) was done 28 days after the last treatment. Hippocampal tissue was removed for biochemical analysis. Production of nitric oxide (NO) and reactive oxygen species (ROS), expression of BDNF/VEGF and cell viability were measured using Griess, fluorimetry, Western blotting and MTT techniques.Results:Different concentrations of silibinin improved behavioral performance in animals. Higher doses of Silibinin could improve memory and learning function through MWM. Also, increasing the concentration of silibinin resulted in decreased ROS and NO production in a dose-dependent manner.Conclusion:Consequently, silibinin may act as a potential candidate for alleviating symptoms of AD.