Hypertension is one of the co-morbid conditions for stroke and profoundly increases its incidence. Angiotensin II (AngII) is shown to be at the center stage in driving the renin angiotensin system via activation of angiotensin 1 receptor (AT1R). This makes the AT1R gene one of the candidates whose differential regulation leads to the predisposition to disorders associated with hypertension. A haplotype block of four SNPs is represented primarily by haplotype-I, or Hap-I (TTAA), and haplotype-II, or Hap-II (AGCG), in the promoter of human AT1R (hAT1R) gene. To better understand the physiological role of these haplotypes, transgenic (TG) mice containing haplotype-I and II of the hAT1R gene in a 166Kb BAC (bacterial artificial chromosome) were generated. Mice received injection of endothelin-1 (1mg/ml) directly in to the striatum and were evaluated for neurologic deficit scores and sacrificed for analysis of infarct volume and mRNA levels of various proteins. Mice containing Hap-I suffered from significantly higher neurological deficits (50%) and larger brain infarcts (60%) than Hap II. Similarly, the molecular analysis of oxidant and inflammatory markers in brains of mice showed a significant increase (p<0.05) in NOX-1 (2.3 fold), CRP (4.3 fold) and IL6 (1.9 fold) and a corresponding reduced expression of antioxidants SOD (60%) and HO-1 (55%) in Hap-I mice as compared to Hap-II mice. These results suggest that increased expression of hAT1R rendered Hap-I TG mice susceptible to stroke-related pathology, possibly due to increased level of brain inflammatory and oxidative markers and a suppressed antioxidant defense system.