The bacterial endotoxin, lipopolysaccharide (LPS), is a well-characterized inflammatory factor found in the cell wall of Gram-negative bacteria. In this investigation, a murine RAW264.7 macrophages cell line was used to study the cytotoxic interaction between 2-chloroethyl ethyl sulfide (CEES or ClCH2CH2SCH2CH3) and inflammatory factors such as LPS, TNF-alpha and IL-1beta. CEES is a sulfur vesicating agent and is an analog of 2, 2’-dichlorodiethyl sulfide (sulfur mustard). We also initiated experiments to determine: (1) the extent to which necrosis or apoptosis is responsible for CEES toxicity; (2) the effectiveness of antioxidant liposomes in preventing CEES toxicity to stimulated macrophages. Our results indicate that inflammatory factors increase CEES toxicity to RAW 264.7 macrophages. Very low levels of LPS (20 ng/ml) dramatically enhanced the toxicity of CEES at concentrations greater than 400 μM. The cytotoxic interaction between LPS and CEES reaches a maximum 12 hours after exposure. In addition, tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1-beta) as well as phorbol myristate acetate (PMA) enhanced the cytotoxic effects of CEES. Necrosis was found to be an important mechanism of CEES toxicity to stimulated macrophages at high concentrations of CEES whereas apoptosis was the dominant mechanism at low concentrations of CEES. Antioxidant-liposomes containing either tocopherol (vitamin E), N-acetyl cysteine (NAC) or glutathione (GSH) were found effective in preventing CEES toxicity to stimulated macrophages.