Background: Thallium is a toxic heavy metal. Its salts are tasteless, odorless and easily dissolved in water. It causes serious health hazards which may lead to death. Thallium poisoning can occur even in small doses with any type of contamination and through any route of administration. It distributes in all tissues of the body causing severe tissue damage due to its high affinity to sulfhydryl groups in some amino acids leading to interference with many enzyme systems and proteins of the body. Accidental, occupational and criminal cases of thallium poisoning are continuously attended to health centres all over the world.Prussian blue is the only known effective antidote of thallium poisoning but it should be taken early to exert its maximum effects since its non absorbable and chelate thallium in the intestine and facilitate its excretion with feces. A matter of great urgency to develop other drugs counteract thallium in tissues and reduce its toxic effects for longer time after poisoning. Oxidative effects are part of thallium toxic mechanisms. Zinc sulphate, a well known antioxidant drug with wide biological activity and silymarin, an extract from silybum marianum is a herbal drug with antioxidant effects both were selected to test of antioxidant effect on thallium poisoning.Materials and methods: in this study which was conducted in the animal house of Baghdad college of medicine, the animals were divided into 8 groups each group contains 12 rats as follows: A normal group (A) given 3 ml of distilled water (DW) orally for 5 days, a thallium group (B) given thallium acetate 16 mg/kg dissolved in 3 ml DW in a single oral dose, zinc sulphate pre and post-treatment groups (C & D) given zinc sulphate solution in a dose of 20 mg/kg orally for 5 days before and after single oral thallium acetate solution in a dose of 16 mg/kg , silymarin pre and post-treatment groups(E &F) given oral silymarin dose 25 mg/kg dissolved in 3 ml DW for 5 days before and after single oral thallium acetate solution 16 mg/kg dose , Prussian blue pre and post-treatment groups (G &H) given orally in a dose of 50 mg/kg dissolved in 3 ml DW for 5 days before and after single oral thallium acetate solution 16 mg/kg dose. Animals were under observation for 4 weeks before sacrifice. The following parameters were studied : health parameters (diarrhea, hair loss, piloerection and case fatality rate), neurological tests (righting reflex, grasp reflex, placing response and corneal reflex), liver enzymes (ALT, AST and ALP), renal function tests (urea and creatinine) , serum electrolytes (Na, K, and Cl), serum trace elements (Zn and Cu), serum oxidative state parameters (GSH and MDA) and histopathological study of hepatic, renal and skin tissues. Results: thallium had caused a significant toxic changes (P < 0.05) in majority of parameters studied. Zinc sulphate had caused significant beneficial changes (P < 0.05) in piloerection, case fatality rate, grasp reflex , placing response, S. ALT, S. AST, S. creatinine, S. zinc, S. copper, S. potassium and S. MDA. In addition, zinc sulphate had a protected tissues and minimized thallium toxic histopathological effects. Silymarin also had caused significant beneficial changes (P < 0.05) in S. ALT, S. AST, S. creatinine, S. GSH and S. MDA. Histopathological study had shown that silymarin reduced thallium toxic effects on the tissues particularly liver. Prussian blue had caused significant changes (P < 0.05) in majority of parameters studied. All health parameters, neurological tests were changed significantly. Also, S. ALT, S. urea , S. creatinine, S. GSH and S. MDA had shown significant changes. In all drugs above significant changes occurred more frequently in post-treatment than pre-treatment group. Conclusion : the results obtained in the present study clearly had shown the beneficial effects of using zinc sulphate, silymarin and Prussian blue when used pre- and post-treatment in reducing toxic effects of thallium on different tissues in the rat body.