Detailed chemistry represents a fundamental pre-requisite for a realistic simulation of combustion process in Diesel engines to properly reproduce ignition delay and flame structure (lift-off and soot precursors) in a wide range of operating conditions. In this work, the authors developed reduced mechanisms for n-dodecane starting from the comprehensive kinetic mechanism developed at Politecnico di Milano, well validated and tested in a wide range of operating conditions . An algorithm combining Sensitivity and Flux Analysis was employed for the present skeletal reduction. The size of the mechanisms can be limited to less than 100 species and incorporates the most important details of low-temperature kinetics for a proper prediction of the ignition delay. Furthermore, the high-temperature chemistry is also properly described both in terms of reactivity and species formation, including unsaturated compounds such as acetylene, whose concentration controls soot formation.The consistency between reduced and detailed mechanism was verified in several reference experiments. Then, the mechanism was applied to diesel spray combustion modeling. Simulations were performed by using the Lib-ICE code, entirely developed by the authors and based on OpenFOAM technology. To evaluate the predictive capability of the reduced mechanisms, combustion simulations were performed using the MRIF (Multiple Representative Interactive Flamelets) model. Such model approximates the flame structure as a set of multiple unsteady flamelets and their evolution is computed in the mixture fraction space, where species and energy equations are solved. Experimental data from the Engine Combustion Network Database were used for validation, by comparing computed and experimental data of flame-lift off and ignition delay at different operating conditions.