Endogenous nitric oxide (NO) is a potent vasodilator that regulates vascular tone. There is evidence that cigarette smoking increases superoxide production in blood vessels by rapidly inactivating NO. This impaired NO bioavailability is a critical cause of endothelial dysfunction and a major risk factor for vascular disease, such as hypertension and atherosclerosis. Quantitative measurement of the NO decay rate in the blood of cigarette smoke treated animals is important for understanding the effect of cigarette smoking on NO decay kinetics in the vasculature. Carbon fiber microelectrodes (CFM) have been used for measurements of NO concentration. However, the time course of recorded current changes (I-t curves) by a CFM is different from the actual time course of NO concentration changes (c-t curves) due to CFM's response time (several seconds). This complicates the determination of rate constants for NO decay from the I-t curves. To find a simple method for analyzing experimental data, we present a mathematical model to describe the relationship between the recorded currents at the CFM and the NO concentrations in the solution. Using computer simulations based on the mathematical model, an approximation method was developed for determining the rate constants of NO decay from I-t curves, and the measurement accuracy was determined. This method was tested in several simple reaction systems with known rate constants, and applied to measure the rate constants of NO decay in blood samples of cigarette smoke exposed and control unexposed mice. These measurements demonstrate that smoking exposure increases the rate of NO decay in blood due to leukocyte activation with superoxide generation.