Background: Amiodarone (AD), the most effective anti-arrhythmic drug, has been reported to cause optic neuropathy, which may result in permanent visual loss. Aim of the work: The current study aimed to clarify the effect of amiodarone administration on the structure of optic nerve and to evaluate the role of L-Carnitine (LC) in protection against such effect. Materials and Methods: This study was carried out on 20 male rabbits divided into five equal groups (four rabbits each). Group I (control group) received no treatment. Group II received saline. Group III received LC. Group IV received AD. Group V received both LC and AD. Animals of treated Groups (II-V) received daily dose for four weeks, then animals of all groups were sacrificed one day after the last dose. Their optic nerves were subjected to light microscopic, electron microscopic and morphometric studies. Results: After AD administration, there was a significant decrease in the number of total and apparently normal nerve fibers while the apparently degenerated ones were increased. There were areas of thickened perineurium. The myelin sheath showed areas of loss of lamellar pattern, splitting or thickening. Many axons appeared with areas of shrinkage and separation from the myelin sheath. The axoplasm of some fibers looked with inclusion bodies or with disrupted organelles. The astrocytes, oligodendrocytes and microglia cells were increased in number. Some oligodendrocytes appeared degenerated. Some oligodendrocytes and astrocytes looked with swollen mitochondria with disrupted cristae. Concomitant administration of LC with AD has minimized the AD-induced effects on the optic nerve. Conclusion: It is concluded that AD administration caused several degenerative effects in the optic nerve. These degenerative effects were greatly ameliorated by concomitant administration of LC. Thus, it is recommended to use LC with AD for treatment of cardiac arrhythmias.