Introduction: Metals such as silver have special merit in medicine. Recently, it has been shown that silver nanoparticles (Ag-NPs) can present some properties that could be valuable for researchers because of their dual neuroprotective and neurotoxic behaviors. The present study was planned to evaluate the effect of silver nanoparticles on OLN-93 oligodendrocytes through chemical hypoxic situation. Methods: AOLN-93 cell line was selected as an oligodendroglial cell model. The stock of the tested solution contained Ag-NPs with an average size of 40nm and concentration of 20.4 ppm. Chemical hypoxic-ischemic condition was induced by sodium azide (NaN3). After a three-hour pretreatment of OLN-93 cells with Ag-NPs (0.001ppm), the cells were incubated in glucose-free medium with sodium azide (100mM and 1M) and Ag-NPs (0.001ppm) for 15min. Then, the reperfusion condition was set by returning the medium to DMEM with 10% FBS along with Ag-NPs (0.001ppm) for 24h. Next, the viability of the cells was assessed by MTT method. Also, Transmission electron microscopy images were used to evaluate the morphology of the cells. Results: Our results showed that Ag-NPs with a concentration of 0.001 ppm could significantly increase ONL-93 cells survival through the 15min hypoxic-ischemia condition induced by NaN3 (100mM) followed by reperfusion (93.02±2.83). However, Ag-NPs (0.001ppm) could not protect the cells from hypoxic-ischemic injury induced by NaN3 (1M) through the same procedure. Conclusion: Although the neurotoxic effects of Ag-NPs have been documented in many studies, the Ag-NPs solution, which was used in this study, could show protective effects on oligodendroglial cells in concentration of 0.001 ppm during the planned model of chemical ischemia. Hence, more investigation is suggested to clarify the protective effect of Ag-NPs (average size of 40 nm) on oligodendrocytes.