© 2016, Mashhad University of Medical Sciences. All rights reserved.Objective(s): The aim of this study was to evaluate, for the first time, whether the effects of low-dose adropin administration is effective in rats with hyperlipidemia. Materials and Methods: Twenty one Wistar albino female rats were randomly divided into 3 groups and fed with high-fat diet for 4 weeks to establish the hyperlipidemia model. Meanwhile, adropin was administrated intraperitonealy (2.1 μg/kg/day), once a day for continuous 10 days. Then, body weights and serum biochemical parameters, adropin, insulin and blood glucose levels were determined. Additionally, in liver tissue, inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) mRNA gene expressions were evaluated by RT-PCR. Results: The results showed that intraperitoneal administration of adropin to hyperlipidemic rats for 10 days were extremely effective in decreasing the levels of serum triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and gamma glutamil transferase (GGT) and increasing the levels of high density lipoprotein cholesterol (HDL-C). It could decrease mRNA expressions of pro-inflammatory cytokines TNF-α and IL-6 via regulating the expressions of iNOS. In addition, treatment with adropin showed a significant reduction in blood glucose, serum insulin levels, HbA1c (%), and HOMA-IR, and increase in serum adropin levels. Conclusion: Adropin may ameliorate lipid metabolism, reduce insulin resistance, and inhibit hepatocytes inflammation. Thus, adropin had significant therapeutic benefits and could be suggested as a potential candidate agent against hyperlipidemia.