It is known that oxygen tension in tissue (ptO2) will change in response to an alteration of physiological parameters including: pCO2 in arterial blood, blood flow, capillary density, oxygen carrying capacity, and p50 of hemoglobin. We have used modeling to compute the change of PtO2 in response to changes of each physiological parameter and related these changes to experimental data. The oxygen distribution in a Krogh cylinder was computed assuming a linear decrease of hemoglobin saturation from the arterial to the venous end of the capillary. Parameters of the model were used to compute the baseline cerebral PtO2 expressed as the mean value of the PtO2 over the whole cylinder. These parameters were adjusted to derive PtO2 values close to those measured at the relevant experimental conditions. Then each desired parameter was varied to calculate the change in PtO2 related to this parameter. Effects of different factors on cerebral PtO2 were modeled and compared with experimental values obtained with various experimental interventions including: changing CBF, modifying p50 with the allosteric modifier RSR13, modification of capillary density, and hemoglobin content. An acceptable agreement of the computed and the experimental changes of the cerebral PtO2 was obtained for these experimental conditions.