Microparticles (MPs) are small vesicles released from the plasma membrane of activated and/or apoptotic cells. We have previously shown that MPs generated from apoptotic T cells induce endothelial dysfunction through a decrease of nitric oxide production (NO). In this study we hypothesize that the mechanism by which MPs induce endothelial dysfunction implicates endoplasmic reticulum (ER) stress activation. For this, human aortic endothelial cells (HAoECs) are treated with 10μg/ml MPs in the absence or in the presence of the ER stress inhibitor TUDCA for 24 hours. Expressions of molecular components of ER stress such as XBP- 1, p-eIF2alpha and CHOP are increased by MP treatment and are prevented in the presence of TUDCA. In addition, in the presence of inhibitors of reactive oxygen species (ROS) sources (allopurinol, apocynin or rotenone), MPs are not able to induce ER stress indicating the implication of ROS in the effects of MPs. Since during ER stress, it has been shown that ER and mitochondria interactions are increased, we analyzed the expression of mitofusin-2 and VDAC-1 channel, two components of mitochondria-associated membranes. MPs are able to increase expression of mitofusin-2 and to decrease VDAC-1 channel suggesting that mitochondria-associated membranes are implicated in the effects of MPs. Finally, the decrease on NO production induced by MPs is prevented in the presence of TUDCA. Altogether, these results show the involvement of ER stress and the mitochondria in endothelial dysfunction induced by MPs via the increase of ROS production.