Objective: Chronic consumption of nigh fat diet is a primary cause of obesity and metabolic syndrome. Excessive fatty acids induce chronic inflammation in a various tissues and result in metabolic disturbances. In the brain, it has been proposed that hypothalamic inflammation involves in the pathogenesis of obesity and neurodegenerative diseases. However, there have been conflicting results about the direct effect of saturated fatty acids (SFAs) on neuronal cells. To address the question, we evaluated the direct and indirect effect of SFAs on neuroinflammation and insulin resistance using neuronal cells and glial cells. Methods: To determine the direct effect of SFAs on neuronal cells, the cells were incubated with palmitate or stearate, and the mRNA levels of cytokines were evaluated using real-time PCR. Cellular apoptosis and insulin signaling were assessed using Western blotting for caspase-3 and pAKT. To determine the indirect effect of SFAs on neuronal cells, culture supernatants of glia were used. The glial cell culture supernatants were obtained after palmitate or stearate treatment and applied to the neuronal cells. Results: Palmitate and strearate did not increase inflammatory markers such as TNF-alpha, IL-1 beta, IL-6, and IL-8. The culture supernatant significantly increased inflammatory markers in neuronal cells. Palmitate and strearate didn’t induce neuronal apoptosis and insuling resistance. The culture supernatant of glia significantly increased inflammatory markers and insulin resistance in neuronal cells. Conclusion: Saturated fatty acids indirectly induce neuroinflammation and insulin resistance through glial cells in neuron.