Aims: This study aimed to (a) employ our newly designed model, the hypertensive-hypercholesterolemic hamster (HH) in order to find whether a correlation exist between circulating microparticles (MPs), endothelial progenitor cells (EPCs) and their contribution to vascular dysfunction and (b) to assess the effect of irbesartan treatment on HH animals (HHI). Methods and Results: The results showed that compared to control (C) group, HH displayed: (i) a significantly increase in plasma cholesterol and triglyceride concentration, and an augmentation of systolic and diastolic arterial blood pressure, and of heart rate; (ii) a marked elevation of MPs and a significant decrease in EPCs; (iii) structural modifications of arterial wall correlated with altered protein expression of MMP2, MMP9, MMP12, TIMP1, TIMP2 and collagen type I and III; (iv) a considerably altered reactivity of arterial wall closely correlated with MPs and EPC adherence; (v) an inflammatory process characterised by augmented expression of P-Selectin, E-Selectin, vWF, TF, IL-6, MCP-1, RANTES. Additionally, the experiments showed the potential of irbesartan to correct all altered parameters in HH and to mobilize EPCs by NO, chemokines and adhesion molecules dependent mechanism. Conclusions: Hypertension associated with hypercholesterolemia is accompanied by structural modifications and expression of pro-inflammatory molecules by vessel wall, the alteration of vascular tone, enhanced release of MPs and reduced EPCs; the ratio between the latter two may be considered as a marker of vascular dysfunction. Irbesartan that exhibit a pharmacological control on the levels of MPs and EPCs has the potential to restore homeostasis of the arterial wall.