It is known that the biological half-life of silver in the central nervous system is longer than in other organs. However, the potential toxicity of silver nanoparticles (NPs) on brain tissue and the underlying mechanism(s) of action are not well understood. In this study, neurotoxicity of silver NPs was examined in rat after intragastric administration. After a two-week exposure to low-dose (1 mg/kg, body weight) or high-dose (10 mg/kg) silver NPs, the pathological and ultrastructural changes in brain tissue were evaluated with H&E staining and transmission electron microscopy. The mRNA expression levels of key tight junction proteins of the blood brain barrier (BBB) were analyzed by real-time RT-PCR, and several inflammatory factors were assessed in blood using ELISA assay. We observed neuron shrinkage, cytoplasmic or foot swelling of astrocytes, and extravascular lymphocytes in silver NP exposure groups. The cadherin 1 (2(-Delta Delta Ct): 1.45-fold/control) and Claudin-1 (2(-Delta Delta Ct): 2.77-fold/control) were slightly increase in mRNA expression levels, and IL-4 significantly increased after silver NP exposure. It was suggest that silver NP can induce neuronal degeneration and astrocyte swelling, even with a low-dose (1 mg/kg) oral exposure. One potential mechanism for the effects of silver NPs to the nervous cells is involved in inflammatory effects.