A mircoarray analysis was performed to identify novel inflammatory genes that are differentially expressed in the mesenteric arteries of male and female SHR. Fractalkine was found to be the inflammatory gene with the greatest differential expression in mesenteric arteries, with expression being greater in female SHR compared to males. Greater inflammatory mediators in female SHR was verified by measuring urinary MCP-1, TGF- and TNF- excretion, all of which were greater in female SHR compared to males. Real-time PCR, Western blot analysis, and ELISA verified greater soluble fractalkine in mesenteric arteries of female SHR. Consistent with increased fractalkine expression, TACE and TNF- levels in mesenteric arteries were also greater in female SHR. We next tested the hypothesis that mesenteric arteries from female SHR will have greater fractalkine-induced dysfunction. Acetylcholine, sodium nitroprusside, phenylephrine and KCl concentration-response curves were performed in third-order mesenteric arteries from male and female SHR pretreated with either vehicle or fractalkine (1 µg/mL). Fractalkine decreased sensitivity to (1) acetylcholine in arteries from male SHR, (2) phenylephrine in arteries from both sexes, and (3) KCl in arteries from female SHR. In conclusion, urinary and vascular markers of inflammation are greater in female SHR compared to males, although blood pressure and cardiovascular risk are less in females.