Background and Objective: Alzheimer’s disease (AD) is a neurodegenerative disorder specified by deposition of b-amyloid (Ab) and neuronal loss that leads to learning and memory disturbances. One of the most important causes of AD is glutamate-dependent excitotoxicity in brain regions that is vulnerable to AD. According to previous reported results, it was revealed that riluzole, as a glutamate release inhibitor, could improve learning and memory in an experimental model of AD. The aim of this study was to determine the effects of riluzole on Hippocampal astrogliosis and amyloidosis in a rat model of AD. Materials and Methods: In the present study, the effects of riluzole administration at a dose of 10 mg/kg/day p.o. on hippocampal glial fibrillary acid protein (GFAP) as an astrogliosis marker and inducible nitric oxide synthase (iNOS) level in Ab (25-35)-injected rats was evaluated. Results: The results showed that in Ab (25–35)-injected rats, the intrahippocampal GFAP (p<0.05) and iNOS (p<0.0001) level increased as compared to sham group. Administration of riluzole to Ab (25–35)-injected rats could significantly decrease iNOS level (p<0.05) and had no effect on GFAP level. Conclusion: This study indicates that in rat model of AD, riluzole is able to attenuate NO synthesis with reducing hippocampal iNOS level, probably through inhibition of glutamatergic signaling pathway.