This paper proposes a method to measure the reaction rate constants in kinetically-simple pyrolysis systems using rapid compression machine (RCM) and fast sampling. The method involves first performing sensitivity analysis based on a reasonable kinetic model to identify the species dominated by a target reaction. Then the time-resolved species concentration profiles are measured in RCM experiments using fast sampling and gas chromatography. Finally, the pre-assigned pre-exponential factor and the activation energy are optimized by an iterative fitting procedure, in which the entire temperature profile derived from the pressure history is taken into account. In order to validate this method, the rate constant of the reaction CH3OCHO (methyl formate, MF) => CH3OH + CO (R1) was determined by measuring the CO concentration over 948-1112 K at 30 bar, obtaining the rate expression k(R1)/s(-1) = 3.04 x 10(13) exp(-30968 K/T), which is consistent with previous theoretical and experimental studies. The rate constant of the reaction CH3OCOOCH3 (dimethyl carbonate, DMC) => CH3OCH3 (dimethyl ether, DME)+CO2 (R2) was then studied by measuring the time-resolved DME concentration over 994-1068 K at 30 bar. The measured rate expression of k(R2)/s(-1) = 2.02 x 10(13)exp (-34248 K/T) with an uncertainty of +/- 30% agrees well with the RRKM/Master Equation calculation based on a high-level quantum chemical potential energy surface. (C) 2017 The Combustion Institute. Published by Elsevier Inc. All rights reserved.