Weightlessness induces an acute syndrome called the cardiovascular deconditioning, associating orthostatic intolerance with syncope, increase in resting heart rate and decrease in physical capability. Orthostatic intolerance occurs after short term and long term head down bed rest and after long term space flight. Both head down bed rest and space flight induce a significant decrease of the spontaneous baroreflex sensitivity. However, spontaneous baroreflex sensitivity only characterizes the cardiac baroreflex loop. To go further with the analysis of cardiovascular deconditioning we were interested in the microcirculation. As the endothelium plays a crucial role in the regulation of vascular homeostasis and local blood flow, we hypothesized that endothelial dysfunction is associated with bed rest induced changes. We investigated endothelial properties before and after 56 days of bed rest in 8 women of control group and in 8 women who regularly performed physical exercise as countermeasure. Our study shows that prolonged bed rest causes impairment of endothelium-dependent functions at the microcirculation level, along with an increase in circulating endothelial cells. Endothelium should be a target for countermeasures during periods of prolonged bed rest or exposure to weightlessness.