Vesicants (sulfur mustard [HD] and arsenical Lewisite [L]) are agents that generate irritation, blistering, and vesication of the skin, mucous membranes, and lungs. Due to HD's low volatility, it is considered a persistent chemical agent. HD is an alkylating agent and the alkylation of DNA results in strand breaks, triggering activation of a nuclear DNA repair enzyme, PADPRP. Extreme activity of PADPRP depletes NAD+, a critical cofactor and substrate in glycolysis. This leads to a buildup of glucose-6-phosphate, which activates proteases that cleave adherent fibrils connecting the basal epidermal cell layer to the basement membrane. Epithelial cell migration is modulated by cytokines, such as hepatocyte growth factor (HGF), a disulfide-linked heterodimer (90kDa). We have evaluated the potential therapeutic effect of HGF on wound healing of Calu-3 (a model of lung epithelial) and keratinocyte (a model of skin) cell lines exposed to CEES (2-chloroethyl ethyl sulfide; half-mustard surrogate). The two cell lines were plated on tissue culture inserts and transwells to 80% confluency and then wounded with sterile pipet tips. The wound healing of untreated cells and CEES exposed cells were followed by phase contrast microscopy for 8 days post-exposure. To evaluate the effect of HGF on wound repair in these two cell lines, HGF was added 45 minutes after CEES exposure and wound repair was also followed for 8 days post-exposure. We observed that HGF enhanced wound healing of both Calu-3 and keratinocytes, and also wounded cells subsequently exposed to CEES. The % wound closure compared to control, CEES, CEES + HGF was 45%, 36%, and 55% for Calu-3 cells, respectively. For keratinocytes, the wound closure for CEES exposed and CEES exposed treated with HGF was -3% and 36%, respectively. Notably, HGF also decreased CEES induced cell death in both cell lines, although HGF was more effective for Calu-3 cells. HGF enhanced wound healing and decreased cell death in CEES exposed wounds. The overall protein expression levels were approximately equal between the control, CEES exposed, and CEES exposed with HGF treatment, suggesting that the wound healing does not change the overall protein expression, but the proteins are redistributed during the wound healing process. The cytotoxicity of HGF on the cells was tested and found not to be toxic up to 300 mM (highest concentration tested). HGF represents a potential therapeutic that could be incorporated into healing creams for HD.