Background/Aims: The studies in the patients with iron deficiency anemia (IDA) implied the existence of the association of ghrelin with iron or hepcidin levels in the plasma under the pathophysiological conditions. We hypothesized that fasting may be able to affect iron metabolism via ghrelin under the physiological conditions. Methods: We investigated the effects of fasting on serum ghrelin and iron contents in healthy volunteers (23–31 years) and C57BL/6 male mice (8-week-olds) under the physiological conditions. Results: Fasting induced a significant elevation in both total ghrelin and acylated ghrelin and a reduction in iron levels in the serum of both human and mice. Correlation analysis demonstrated that total ghrelin or acylated ghrelin is negatively correlated with iron in the serum in human and mice. Conclusion: Ghrelin has a role to reduce serum iron under the conditions of fasting.