Microparticles (MPs) are plasma membrane vesicles with procoagulant and proinflammatory properties. We recently demonstrated that MPs induce vascular hyporeactivity and evoke upregulation of pro-inflammatory protein expression. This study dissected the effect of either in vitro treatment or short-term oral administration of the peroxysome proliferator activated receptor-γ agonist, rosiglitazone (RZ), on MPs-induced vascular hyporeactivity of mice vessels. MPs were produced from human lymphoid CEM T cells by actinomycin D treatment. The effects of RZ on mice aortic rings incubated with or without MPs were investigated. Both, aortic rings treated in vitro with RZ or taken from mice treated by oral administration of the same agonist, completely prevented MPs-induced vascular hyporeactivity in response to U46619. These effects of RZ occurred at a concentration at which it did not significantly modify blood parameters and vascular reactivity. The mechanisms involved abrogation of nitric oxide (NO) and prostacyclin overproduction linked to upregulation of inducible NO-synthase and cyclo-oxygenase 2 elicited by MPs. Also, RZ treatment attenuated the ability of MPs to evoke NF-κB activation. These results suggest that RZ counteracts vascular dysfunction associated with increase release of pro-inflammatory proteins elicited by MPs. They underscore therapeutic perspective for RZ in vascular diseases involving enhanced participation of MPs.