OBJECTIVE: Sulphur mustard (SM), chemically 2,2′-dichloro diethyl sulphide, is an incapacitating and extremely toxic chemical warfare agent, and causes serious blisters on contact with human skin. SM forms sulphonium ion in the body that alkylates DNA and several other macromolecules, and induces oxidative stress. The aim of this study was to evaluate the protective effect of Aloe vera L. gel ... [Show full abstract] against SM-induced systemic toxicity and skin lesions. MATERIALS AND METHODS: Aloe vera gel was given (250, 500 and 1000 mg/kg) orally to mice as three doses, one immediately after SM administration by percutaneous route, and the other two doses on the next two days. Protective index was calculated with and without Aloe vera gel treatment. Aloe vera gel was also given orally as three doses with 3 LD50 SM and the animals were sacrificed for biochemical and histological evaluation, 7 days after SM administration. In another set of experiment Aloe vera gel was liberally applied on the SM administered skin site and the animals were sacrificed after 14 days to detect its protective effect on the skin lesions induced by SM. RESULTS: The protection given by Aloe vera gel was marginal. 1000 mg/kg dose of Aloe vera gel gave a protection index of 2.8. SM significantly decreased reduced glutathione (GSH), oxidised glutathione (GSSG) and WBC count, and significantly increased malondialdehyde (MDA) level, RBC count and Hb concentration. Aloe vera gel offered protection only in the increase of MDA level by SM. Severe damage was observed in the histology of liver, spleen and skin following SM administration, and 1000 mg/kg of Aloe vera gel partially protected the lesions. However, topical application of Aloe vera gel showed better protection of the skin lesions induced by SM. CONCLUSION: The study shows that percutaneous administration of SM induces oxidative stress and oral administration of Aloe vera gel could only partially protect it. Topical application of Aloe vera gel may be beneficial for protecting the skin lesions induced by SM.