Chronic respiratory disorders such as asthma are believed to be associated with adverse cardiovascular events. We hypothesize that asthmatic inflammation translates into systemic inflammation and alters vascular responses where adenosine (AD) plays an important role. Therefore, this study investigated the effects of aerosolized AD (also well-known in amplifying lung inflammation) on vascular reactivity and systemic inflammation in our allergic mouse model of asthma. Balb/c mice were divided into 3 groups: Control (CON), control+ aerosolized AD (CON+AD),allergen sensitized and challenged (SEN), and SEN+ aerosolized AD (SEN+AD). Animals were sensitized with ragweed (200 µg, i.p.) on days 1 and 6, followed by 1% ragweed aerosol challenges through days 11 to 13. On day 14, CON+AD and SEN+AD group received a single AD aerosol challenge (6mg/ml) for 2 min, followed by collection of aorta and plasma on day 15. Organ bath experiments showed concentration dependent aortic relaxations to AD in CON and CON+AD , which were impaired in SEN and SEN+AD. Real time PCR data showed changes in aortic adenosine receptors (AR), with A₁AR gene expression being upregulated while A₂ARs and eNOS genes expression being downregulated, resulting in impairment of vasorelaxation in SEN and SEN+AD. A₁ AR antagonist (DPCPX) reversed the impairment in vasorelaxation observed in SEN and SEN+AD, while A_2B AR antagonist (alloxazine) inhibited vasorelaxation in all groups. Allergen challenge caused systemic inflammation in allergic mice with AD aerosol further enhancing it as determined by inflammatory cytokines profile in plasma. In conclusion, asthmatic mice showed altered vascular reactivity and systemic inflammation, with AD aerosol further exacerbating these effects.