Smoking is known to be accompanied with a decrease in nitric oxide (NO) bioavailability in the vascular system. This study investigated whether chronic administration of cigarette smoke extract (CSE) influences on soluble guanylate cyclase (sGC) redox state, a determinant of NO bioavailability. Rats were subcutaneously administered phosphate saline buffer (PBS), gas phase-CSE (gp-CSE) or whole phase-CSE (wp-CSE) for 4 weeks, and vascular reactivity was examined in organ chamber experiments. In both the aorta and pulmonary artery, the relaxant response to acetylcholine was attenuated to a similar extent by administration of gp-CSE or wp-CSE. On the other hand, regardless of vessel type, sodium nitroprusside (reduced sGC stimulant)-induced and BAY 60-2770 (oxidized/heme-free sGC stimulant)-induced relaxation were identical in the three groups. These findings suggest that chronic CSE administration induces endothelial dysfunction but has no significant impact on vascular sGC redox state.