Amiodarone (AMR) is a very powerful and efficient anti-arrhythmic agent since it outperforms other treatments in preventing and treating ventricular and supraventricular dysrhythmias. Melatonin is produced by a variety of organs, including the pineal gland. It has anti-oxidant and antiinflammatory properties. Curcumin provides a variety of different health benefits and has been demonstrated to have considerable antioxidant action. The purpose of this study was to look into and evaluate the preventive benefits of melatonin and curcumin against AMR-induced lung damage. 60 adult male albino rats were utilized in this study divided equally into 5 main groups: (control with no drugs, sham divided into 2 subgroups sham1 receiving 500Ug/kg body weight (BW) of melatonin and sham2 receiving 200 mg/kg BW of curcumin, AMR treated group receiving 40 mg/kg BW of AMR orally, AMR with melatonin group receiving500Ug/ kg body weight (BW) of melatonin and40 mg/kg BW of AMR, and AMR with curcumin group receiving 200 mg/kg BW of curcumin and 40 mg/kg BW of AMR). this study was continued for 6 weeks. The lung tissue was processed for histopathological and biochemical evaluation at the end of the experiment. Revealed significant elevations in inflammatory cytokine (il6) and oxidative parameters, lung alterations with fibrosis and marked cellular infiltration in the AMR-treated group. Yet treatment with melatonin and curcumin improved fibrosis detected by decreased area of positive TGF-â1 staining and lower number of stained macrophages by CD68 along with improving the antioxidant status of the tissue. Thus melatonin and curcumin had a protective effect over AMR-induced fibrosis