This study aims to investigate the oxidative stress role in the pathogenesis of amiodarone-induced pulmonary toxicity and to show whether antioxidants´ coadministration with amiodarone could exert any protective effect. The study was carried out on 36 Sprague-Dawley males, rats were divided into the following six equal groups, drugs were given by gastric tube every day for 7 days as follow; control group: received distilled water, amiodarone (AM) treated group: received amiodarone (100 mg / kg body weight), L-carnitine (LC) treated group: received L-carnitine (100 mg/kg body weight), vitamin C treated group: received vitamin C (1 mg/100 g body weight), amiodarone and L-carnitine treated group: received amiodarone along with LC and amiodarone and vitamin C treated group: Received amiodarone together with vitamin C. The histopathological findings showed that amiodarone disrupted lung architecture and caused inflammatory cells infiltration in addition to extensive fibrosis. Increased level of Malondialdehyde (MDA) and decreased level of catalase (CAT) in lung tissue homogenates were observed in the AM-treated group. Administration of L-carnitine and vitamin C improved the biochemical and histopathological alterations in the lungs induced by amiodarone. Vitamin C was more protective than LC as regard the histopathological changes. Antioxidants administration induced a significant decrease in MDA and an increase in CAT in lung tissue as compared with AM treated group. The oral administration of LC and vitamin C reversed the biochemical and histopathological alterations induced by AM. They may have a protective role in the AM-induced lung toxicity.