Background/Aims: Alarin has been reported to be related with increased food intake and body weight. The relationship of circulating Alarin with insulin resistance or metabolic syndrome (MetS), however, is unknown. This study aimed to investigate the physiological role of Alarin and its association with MetS in humans. Methods: Newly diagnosed MetS patients (n=237) and age-matched healthy subjects (n=192) were recruited for this study. Oral glucose tolerance test, treadmill exercise, lipid infusions and euglycemic-hyperinsulinemic clamp (EHCs) were performed. Circulating Alarin and TNFα levels were measured by ELISA. Results: Circulating Alarin levels were significantly higher in MetS patients compared with healthy subjects (0.46 ± 0.22 vs. 0.41 ± 0.14 µg/L, P < 0.01). In all studied subjects, circulating Alarin levels were positively correlated with WC, blood pressure, FBG, triglyceride, HbA1c, HOMA-IR, AUCglucose, and TNFα (P < 0.05 or P < 0.01). Multivariate logistic regression analyses revealed that circulating Alarin levels were correlated with MetS and insulin resistance. There was no significant change of circulating Alarin levels in the subjects with treadmill exercise for 45 min. In healthy individuals, however, glucose challenge, acute hyperglycemia and lipid infusions resulted in increased circulating Alarin levels, while acute hyperinsulinaemia transiently decreased circulating Alarin levels. Conclusion: The present study provides the evidence that circulating Alarin levels are associated with MetS and insulin resistance.