We aimed to evaluate serum vaspin and its gene expression in patients with type 2 diabetes mellitus (T2DM) and to assess the association of serum vaspin and its gene expression with susceptibility of ischemic stroke (IS). The prospective case-control study included 50 healthy individuals in a control group, and 90 patients with and T2DM were stratified into two subgroups: patients with IS and patients without IS. The serum vaspin concentration was measured by enzyme-linked immunosorbent assay (ELISA). Real-time PCR was performed to detect the mRNA expression of vaspin. Serum vaspin and vaspin expression levels were significantly higher in IS compared to the non-IS group. Interestingly, they were positively correlated with other vascular and metabolic risks. Diastolic and systolic blood pressure, as well as haemoglobin A1c (HbA1c), cholesterol, were independently correlated with serum vaspin. After adjusting for the traditional risk factors, the logistic regression analysis test was done to evaluate the predictor of IS among T2DM patients; the vaspin expression level was a statistical significance predictor of IS among T2DM patients. In conclusion, the higher levels of serum vaspin and vaspin expression levels in T2DM emphasizes the pivotal role of vaspin serum level and expression in the progression of metabolic and glucose abnormalities, thus, they could be used as biomarkers of IS.