ABSTRACT. Ischemic stroke (IS) is a multifactorial disorder, and genetic factors act as important contributors to its onset and progression. Inflammation is a key event that is closely associated with the pathophysiology of IS. The association of genetic polymorphisms of inflammatory cytokines with IS remains poorly understood. We investigated the relationship between the variable number of tandem repeats (VNTR) for IL-4, which is an important biomarker of inflammation, and the risk of IS. To assess the nature of the VNTR polymorphism in IL-4 and identify any links with IS, we recruited 200 subjects from a unique population that has 60% European and 40% East Asian ancestry. The subjects comprised 100 IS patients diagnosed using magnetic resonance imaging within 24 h of symptom onset and 100 age-, gender-and ethnicity-matched normal healthy controls. VNTR was identified using high-performance capillary electrophoresis with specially designed tailed primers. The IL-4 VNTR polymorphism was significantly associated with IS after adjustment for cardiovascular risk factors (OR = 0.571, 95%CI = 0.330-0.949, P < 0.05). Our data indicate that IL-4 VNTR polymorphism may affect susceptibility to IS in the Chinese Uyghur population. Moreover, total cholesterol, fasting blood glucose, waist-to-hip ratio, hypertension, history of heart diseases, and negative events may increase the risk of IS, with a trend for HDL to be a protective factor for IS in the Uyghur population.