Free radical formation and release of oxidant agents have been suggested as possible mechanisms for tissue damage in acute iron intoxication. N-acetylcysteine (NAC), a glutathione substitute and an antioxidant, is widely used as an antidote for various intoxications. Our aim was to determine whether intraperitoneal (i.p.) NAC would reduce the mortality of rats after acute, toxic oral doses of iron. Male Wistar rats were studied in three phases. In the first phase, animals were assigned to groups 1 (distilled water by gavage) and 2 (i.p. NAC) and observed for survival. In the second phase, rats were assigned to groups 3 (400 mg/kg elemental iron orally) and 4 (400 mg/kg elemental iron, followed by 150 mg/kg i.p. NAC). Survival was observed. Because most rats in Group 3 died within 90 minutes after iron administration, a third phase was conducted in order to allow for comparison of iron and transaminase serum levels after the administration of iron and NAC (group 5: n = 10). Mortality was significantly lower in rats treated with iron and NAC, compared to those treated with iron (P = 0.016). Median serum iron level was significantly lower among rats treated with iron and NAC, compared with rats treated with iron alone (P = 0.002). In a rat model of acute iron intoxication, i.p. administration of NAC may decrease serum iron levels and mortality.