Stroke remains the leading cause of severe disability and the third leading cause of death after heart disease and cancer. Stroke is a complex multifactorial disorder that is thought to result from an interaction between a person`s genetic background and various environmental factors . This study aimed to evaluate the association of IL-18137G polymorphism and high sensitivity (hs) C-reactive protein ( CRP) with risk in acute ischemic stroke (AIS )and their relationship with subtypes and severity of stroke. 106 patients with acute ischemic stroke in addition to 97 age and sex matched healthy controls were evaluated for genetic polymorphism of IL-18137G/C by PCR -sequence specific primer and hs CRP by nephelometry using BN prospec system . Results showed significant association of 137/CC genotype with increased risk of acute ischemic stroke ( OR= 2.131, 95%CI=2.559). Similar results were observed in large artery atherosclerosis(LAA) and cardioembolic (CE) subtypes (OR=3.226,95%CI=2.408-4.321 and OR=8.667,95%CI=4.688-16.022,respectively) and severity of stroke (p=0.004). CRP levels on admission were significantly higher in AIS patients than controls (p=<0.001). Also as they were associated with increased risk of AIS (or=4.880, 95%CI=3.440-6.922) ,all subtypes (or=8.462,95%CI=5.o79-14.097 for LAA, or=10.700,95%CI=5.931-19.305 for small vessel disease (SVD) and or=49.500,95%CI=12.55-195.157 for CE subtype and severity (p=0.013). Conclusion IL-18137G/C polymorphism and CRP acting together as inflammatory and atherosclerotic players in the progression of cerebral tissue injury.