Sodium methyldithiocarbamate (SMD) is commonly reported to cause health risks in humans. Previous reports indicate SMD causes oxidative stress, which can contribute to the activation of NF-êB and cause other characteristics of inflammatory responses to be altered. Almost all pro-inflammatory cytokines require NF-êB activation for full expression and development of an innate immune or inflammatory response. This study evaluated NF-êB activation, providing new information regarding reactive oxygen in macrophages from SMD-treated mice. Studies were conducted in which NF-êB reporter mice were treated with lipopolysaccharide (LPS), SMD, buthionine sulfoximine (BSO), and N-acetyl cysteine (NAC). BSO depletes glutathione (GSH) and increases oxidative stress, whereas NAC spares GSH by acting as a precursor for rapid synthesis to replace oxidized GSH. The work here indicates that NF-êB is not affected directly by increased or decreased reactive oxygen species (ROS), and oxidative stress is not the major mechanism by which SMD inhibits inflammatory responses.