Background: Migraine is considered a disabling neurovascular disorder. The exact pathophysiological mechanism underlying migraine headache is still incompletely understood Activation of meningeal afferents, neuopeptide release and neurogenic inflammation play a pivotal role in the generation of pain in migraine headache. Lipocalin-2 (LCN2), a secretory protein, regulates diverse cellular processes such as cell death/survival, inflammation and tissue regeneration. LCN2 is also secreted by brain astrocytes under inflammatory conditions and promotes apoptosis, morphological changes and migration in astrocytes both in vitro and in vivo and acts as a proinflam-matory mediator in the central nervous system. Aim of the work: To assess the serum level of LCN2 in migraine patients and its association with the systemic inflammatory mediators. Subjects and methods: This study was conducted during the period between March, 2016 and November, 2016 in Outpatient Clinics of Zagazig University Hospitals on 60 ageweight matched individuals. They were divided into 2 equal subgroups. Group (I): Control without headache and group (II): Was further subdivided into 2 groups; group (IIa): Migraine patients without aura (MWoA) and group (IIb): Migraine patients with aura (MWA). For each group, serum LCN2, C Reactive Protein (CRP), Tumor Necrosis Factor- a (TNF-a), bilirubin, Triglyceride (TG), High Density Lipoprotein Cholesterol (HDL-c) and Atherogenic Index of Plasma (AIP) were measured. Results: In group IIa (MWoA): LCN2, CRP and TNF- a levels were significantly higher than that of group I, while total bilirubin and direct bilirubin were significantly lower than that of group I. In group IIb (MWA): LCN2, CRP, TNFa , TG levels and AIP value were significantly higher than that of group I and IIa, while total bilirubin and direct bilirubin were significantly lower than that of group I and IIa. However, there was a non-significant difference in serum HDL-c between groups. Conclusion: Serum LCN 2 plays a role in connecting the inflammatory condition characterizing migraine with stress and atherogenesis. Key words: Migraine – Lipocalin-2 (LCN2) – Inflammation.