Sulphur mustard (SM) is a chemical warfare agent that causes serious blisters upon contact with human skin. SM alkylates DNA and several other macromolecules, and also induces oxidative stress. Quercetin, a bioflavonoid has wide pharmacological actions. The protective efficacy of quercetin (100 mg/kg, i.p. and 200 mg/kg, i.p.) was studied by administering three doses in mice against SM. The first dose was administered at 30 min prior, simultaneous, 2 h post or 24 h post, and two more doses on the next two days. SM was administered (in PEG 300) percutaneously at varying doses for survival and protection studies. SM was also administered at a dose of 2 LD50 (19.3 mg/kg) with and without quercetin treatment and various biochemical markers were estimated 7 days after SM administration. Histological examinations of vital organs were also carried out. The animals administered with SM died at various days depending upon the dose. The body weight decreased significantly, Quercetin protected the mice significantly, in a dosedependent manner. The protection was better when the first dose of quercetin administered was 30 min prior or simultaneously. A significant decrease in reduced as well as oxidised glutathione and an increase in malondialdehyde, WBC count, RBC count, and haemoglobin were observed with 2 LD50 SM. Quercetin at 100 mg/kg and 200 mg/kg doses significantly protected the biochemical markers when the first dose of quercetin administered was 30 min prior or as simultaneous treatment. The histological lesions induced by sulphur mustard on liver, spleen, and skin were also significantly protected by quercetin when the first dose was administered 30 min prior or as simultaneous treatment. The present study shows that percutaneous administration of SM induces oxidative stress and quercetin can protect it as a prophylactic agent. © 2007, DESIDOC.