Oxygen plays a critical role in determining the initial DNA damages induced by ionizing radiation. It is important to mechanistically model the oxygen effect in the water radiolysis process. However, due to the computational costs from the many body interaction problem, oxygen is often ignored or treated as a constant continuum radiolysis-scavenger background in the simulations using common microscopic Monte Carlo tools. In this work, we reported our recent progress on the modeling of the chemical stage of the water radiolysis with an explicit consideration of the oxygen effect, based upon our initial development of an open-source graphical processing unit (GPU)-based MC simulation tool, gMicroMC. The inclusion of oxygen mainly reduces the yields of [Formula: see text] and [Formula: see text] chemical radicals, turning them into highly toxic [Formula: see text] and [Formula: see text] species. To demonstrate the practical value of gMicroMC in large scale simulation problems, we applied the oxygen-simulation-enabled gMicroMC to compute the yields of chemical radicals under a high instantaneous dose rate [Formula: see text] to study the oxygen depletion hypothesis in FLASH radiotherapy. A decreased oxygen consumption rate (OCR) was found associated with a reduced initial oxygen concentration level due to reduced probabilities of reactions. With respect to dose rate, for the oxygen concentration of 21% and electron energy of 4.5 [Formula: see text], OCR remained approximately constant (∼0.22 [Formula: see text]) for [Formula: see text]'s of [Formula: see text], [Formula: see text] and reduced to 0.19 [Formula: see text] at [Formula: see text], because the increased dose rate improved the mutual reaction frequencies among radicals, hence reducing their reactions with oxygen. We computed the time evolution of oxygen concentration under the FLASH irradiation setups. At the dose rate of [Formula: see text] and initial oxygen concentrations from 0.01% to 21%, the oxygen is unlikely to be fully depleted with an accumulative dose of 30 Gy, which is a typical dose used in FLASH experiments. The computational efficiency of gMicroMC when considering oxygen molecules in the chemical stage was evaluated through benchmark work to GEANT4-DNA with simulating an equivalent number of radicals. With an initial oxygen concentration of 3% (∼105 molecules), a speedup factor of 1228 was achieved for gMicroMC on a single GPU card when comparing with GEANT4-DNA on a single CPU.