Background: Metabolic abnormalities and immune dysregulations are the most common risk factors for polycystic ovary syndrome (PCOS). Interleukin-22 (IL-22) is implicated in the pathogenesis of the immune inflammatory system in the context of metabolic dysfunction. In the current research, we aimed to investigate IL-22 mRNA in PCOS and explore its correlations with metabolic syndrome (MetS) and reproductive features of PCOS. Methods: we conducted our research on 60 women as control groups, and 70 patients with PCOS (30 patients without MetS and 40 patients with MetS). We investigated serum IL-22 by ELISA. At the same time, the IL 22 mRNA level was analyzed by RT-qPCR. Results: Among 70 women with PCOS, 40 (57.1%) had metabolic syndrome. women with PCOS had significantly lower serum and mRNA Expression Levels of IL-22 compared to control. Even more importantly, among PCOS patients, women with MetS had significantly lower serum and mRNA Expression levels of IL-22 compared to women without MetS. serum and mRNA Expression levels of IL-22 were negatively associated with MetS components and inflammatory markers as well as reproductive features of PCOS. The AUC of serum and mRNA levels of IL-22 in the prediction of MetS among PCOS women had a sensitivity of 90%, and 77.5%, respectively, and specificity of 66%, 87.3% and respectively. Conclusion: PCOS patients had significantly serum and mRNA Expression levels of IL-22 than controls. the lowered IL-22 serum and mRNA levels could be used as diagnostic markers of PCOS patients more specifically women with MetS.