Background: Gestational diabetes mellitus (GDM) is a pregnancy complication characterized by insulin resistance. Irisin is a myokine that has been associated to obesity and inflammation. The data on irisin levels in pregnancy and GDM is still debatable. Objective: to assess serum irisin levels and explore its association with some metabolic and inflammatory parameters in normal pregnant and GDM rats. Methods and materials: forty-five female albino rats were randomly divided to 3 groups (n=15 animals). The rats of both normal pregnant and GDM-induced groups fed normal diet and Fatty-sucrose diet respectively for five weeks before pregnancy induction. The later injected with streptozotocin on 7th day of gestation. Body mass index (BMI), serum irisin, triglycerides, total cholesterol, low-density lipoprotein-cholesterol (LDL-c), and high-density lipoproteins-cholesterol (HDL-c), c-reactive protein (CRP), glucose, insulin levels and calculated homeostatic model assessment of insulin resistance index (HOMA-IR) were estimated. Results: The irisin levels in normal pregnant rats increased significantly more than in controls, whereas it was significantly lower in GDM rats. In GDM rats, BMI, CRP, glucose, and lipid indices, all were significantly raised and negatively linked with irisin. In GDM rats, HDL-C levels were decreased significantly and positively associated with irisin. Conclusion: Late pregnancy is associated with high serum irisin levels that were lower in GDM rats compared to the normal pregnant rats and negatively correlated with insulin resistance, lipid, and inflammatory parameters.