A method based on the sensitivity analysis and quasi-steady state assumption was systematically developed in this paper to simplify complex reaction mechanisms. A constant pressure homogeneous reactor model and a detailed reaction mechanism were adopted to calculate the auto-ignition process under the interested condition. Then the result obtained with the detailed mechanism was analyzed through the sensitivity analysis and the redundant species and reactions were identified and deleted from the detailed mechanism to form the skeletal mechanism. After that, the quasi-steady state species (QSSS) which were very small and fast were also found from the skeletal mechanism. The global reaction mechanism was derived with some matrix relations from the skeletal one. Finally, the detailed mechanism GriMech1.2 for methane oxidization was simplified to form skeletal and global mechanism as an example, and the result was validated with a comparison with the one obtained with the detailed mechanism.