Background: 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 anti-inflammatory properties. Curcumin provides a variety of different health benefits and has been demonstrated to have considerable antioxidant action. Aim of the study: The purpose of this study was to look into and evaluate the preventive benefits of melatonin and curcumin against AMR-induced lung damage. Material and methods: 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. Results: 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. Conclusion: Thus melatonin and curcumin had a protective effect over AMR-induced fibrosis