Iron is a one of the heavy metals that is necessary for cell function. Acute or chronic exposure to high dose lead to oxidative damage. In the liver, iron overload affect hepatic mitochondrial respiration. Deferoxamine is the established antidote of iron toxicity which act as a chelator. N-acetylcysteine is a safe over the counter mucolytic which is antioxidant and glutathione substitute properities. Its use as an antidote for some toxins is well established nowadays. The aim of this work is to study the efficacy of intravenous N-acetylcysteine as an adjuvant therapy with deferoxamine in acute iron intoxication in rats. This study was carried out on twenty male albino rats, weighted 200-250 gm and divided into group I: 10 rats received 400 mg/kg elemental iron orally followed by 25 mg/kg subcutaneous deferroxamine and group II: 10 rats received 400 mg/kg elemental iron followed by 150 mg/kg IV NAC and 25 mg/kg subcutaneous deferroxamine. The results revealed that N-acetylcysteine use lowered both oxidative stress markers malondialdehyde MDA and cyclic adenosine monophosphate cAMP. On the other hand, the reduction of serum and hepatic iron levels and the elevation of Alanine Transaminase (ALT) and Aspartate Aminotransferase (AST) were statistically insignificant. It was concluded that intravenous N-acetylcysteine helps in reduction of oxidative stress caused by acute iron toxicity.