A review of recent experimental investigations on the nanomechanical response of individual endothelial cells to inflammation caused by environmental agents and selected chemical compounds is presented. We focus on the results obtained by means of the force spectroscopy using the tip of an atomic force microscope as an imaging and nanoindentation spectroscopic probe. The findings presented in this review allow validating the nanoindentation method as a tool for quantitative cell elasticity probing and thereby allow proposing a nanomechanical model of endothelial dysfunction that could be practically used for drug efficacy and toxicity profiling in the endothelium at the subcellular level.