Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary and systemic inflammation. In particular, the clinical course of this disease typically leads to periodic exacerbation involving inflammatory response and both respiratory and cardiovascular symptoms. Even though the exact mechanisms underlying the pathogenesis of COPD and its chronic and acute inflammation have not yet been fully understood, many studies have been highlighting the role of the endothelium, platelets (PTL) and other circulating blood cells. PLT are crucial for hemostasis and, once activated by a number of different factors, will mediate endothelium adhesion, and the rolling and activation of other circulating cells, such as neutrophils, which become a cause of tissue damage during the inflammatory process. The aim of this review is to highlight the onset of activation, thrombus formation and inflammatory amplification with particular regard to the COPD patients and the course of their acute exacerbations.