Methidathion (MD) is one of the most widely used organophosphate insecticides (OPIs) for public health programmes and agricultural purposes. However it causes side effects such as liver disorders. We examined the ameliorating effects of a combination of vitamins E and C against MD induced liver toxicity in rats. MD was given orally with a single dose of 8 mg/kg body weight at 0 h. Vitamin E and vitamin C were injected 30 min after the treatment of MD at doses of 150 mg/kg body weight i.m. and 200 mg/kg body weight i.p., respectively. Liver tissue samples were taken 24 h after the MD administration. In MD treated group, some histopathological changes like infiltration with mononuclear cells at parenchymal tissue, sinusoidal dilatation, focal necrotic areas, granular degeneration and picnotic nuclei in the hepatocytes were observed. The severity of these lesions was reduced by administration of vitamins. It is concluded that MD caused liver damage and single-dose treatment with a combination therapy of vitamins E and C after the administration of MD can reduce the toxic effects of MD on liver tissue of rats.