This paper describes modeling of degradation behavior of high-temperature polymers under thermo-oxidative aging conditions. Thermo-oxidative aging is simulated with a diffusion-reaction model in which temperature, oxygen concentration, and weight-loss effects are considered. A parametric reaction model based on a mechanistic view of the reaction is used for simulating reaction-rate dependence on the oxygen availability in the polymer. Macroscopic weight-loss measurements are used to determine the reaction and polymer consumption parameters. The diffusion-reaction partial differential equation system is solved using Runge-Kutta methods. Simulations illustrating oxidative layer growth in a high-temperature PMR-15 polyimide resin system under isothermal conditions are presented and correlated with experimental observations of oxidation layer growth. Finally, parametric studies are conducted to examine the sensitivity of material parameters in predicting oxidation development.