Monosodium glutamate (MSG), a flavor enhancer, and butylated hydroxyanisole (BHA), an antioxidant, are among the most widely used additives worldwide. The present study aims to investigate the inflammatory effect of oral administration of MSG (40mg/kg body weight) and BHA (0.5mg/kg body weight) for 28 days, by evaluating proinflammatory cytokines in serum and NF-κB, Nrf2, CYP2C11, and CYP2J3 gene and protein expression in liver and cerebral cortex in male Wistar rats. Additionally, one group of rats was intraperitoneally injected with lipopolysaccharide (LPS) to induce systemic inflammation. The administration of MSG significantly increased serum levels of proinflammatory cytokines (TNF-α, IL-6, and IL-1β) and NF-κB gene expression in the liver and cortex. Also, the protein levels of the p65-NFkb subunit increased in cytosolic fraction in liver and Nrf2 transcription factor increased in the nuclear fraction in both the liver and cortex. Although we found that CYP2C11 and CYP2J3 mRNA levels were increased by MSG in the liver and cortex, no differences in protein levels were observed compared to controls. In contrast, BHA consumption did not cause inflammation or oxidative stress. Taken together, our findings suggest that MSG consumption induces systemic inflammation and oxidative stress under the evaluated conditions.