Nitric oxide (NO) is a multifunctional biomolecule involved in a variety of physiological and pathological processes, including regulation of blood vessel dilatation and anti-arteriosclerotic effects. However, a large amount of NO is toxic to the host and causes several diseases such as apoptosis, septic shock, and diabetes mellitus. Inducible-form NO synthase is induced in inflammatory diseases, including insulitis and arteriosclerosis. Endoplasmic reticulum (ER) stress pathway was first identified as a cellular response pathway induced by the accumulation of unfolded proteins in ER to preserve ER functions. Later it was found that ER stress pathway is also activated by various cellular stresses to protect cells, but when stresses are severe, apoptosis is induced to remove damaged cells. It is reported that NO and reactive oxygen species disturb ER functions, then ER stress-mediated apoptosis pathway is activated. CHOP/GADD153, which belongs to C/EBP transcription factor family, is induced in this process and mediates apoptosis. ER stress pathway induced by NO can be involved in the pathogenesis of various vascular diseases.