We developed a C57BL/6 mouse ear model of vesicant injury by using 2-chloro-ethyl-ethyl sulfide (CEES) to invesitgate the biochemical and molecular mechanism of injury and to evaluate effective therapeutics. Te inner ear of the mice were exposed to 1, 2, 3, 4, and 5 mL of CEES, for 10 minutes, then decontaminated using sodium hypochlorite or a proprietary decon solution obtained from Dr. Richard K. Gordon. Evaporation of the CEES was minimized by covering with a lid. The mice were alowed to recover for 24, 48, 72 and 96 hours. Similar volumes of saline were used as controls. The wet/dry ratio of punch biopsies showed that edema peaked at 48h after administration of 1mL of CEES. Greater volumes of CEES resulted in reduced edema, probably due to increased necrosis. Necrosis was evident 72-96 h after CEES application. The affected skin became dried and crumpled and easily exfoliated. Injured skin extended beynd the original site of application, indicating that significant diffusion of the vesicant occurred. Histopathology at 24-48 hours in mice given 1 microliter CEES demonstrated acute dermatitis affecting both the inner and outer ear characterized by dermal edema, epidermal necrosis, subepidermal blistering, infiltration of some neutrophils, and minimal myofiber degeneration. Higher volumes of CEES resulted in greater necrosis. By comparison, the back skin injury model showed a central area of deep injury with less spreading. A larger volume of CEES was required to produce significant edema. Three mL of CEES induced edema and erythema at 24 h. The edema peaked at 24-48 h at this dose. Visual observation of the skin also showed maximum swelling at 24-48 h after 3 microliter CEES application. Blister fluid with hemorrhage was observed under injuired skin. Histopathology data showed skin pathology characterized by dermatitis, panniculitis and cellulitis. Although, a higher volume of CEES produced less edema, severe necrosis of the skin or peeling off the skin was not observed in the back model. The CEES injured skin was found to heal on the back model after 4 days. These results demonstrate that the CEES skin injury has different pathology and more severe in the ear model compared to back skin injury indicating that different therapeutic modalities are required for medical countermeasure depending on the location of the vesicant injury.