The addition of 2-methylfuran into diesel has been studied extensively to deal with the fossil energy crisis and reduce pollutant emissions. However, the chemical reaction mechanism of the engine combustion model related to 2-methylfuran is rarely reported. In this study, a reduced 2-methylfuran chemical reaction mechanism was developed by the directed relation graph with error propagation, reaction path analysis, sensitivity analysis and rate of production analysis. Then it was coupled with a diesel mechanism, and the pre-exponential factor A of the Arrhenius equation was adjusted for specific reactions to finally forma reduced 2-methylfuran-diesel mechanism containing 55 species and 190 reactions for application in combustion modeling under engine related conditions. Based on the experimental data in the literature, the predicted ignition delay time and species mole fractions by the mechanism were validated. Also, the three-dimensional simulation data was compared with the test data of cylinder pressure and heat release rate from a single-cylinder diesel engine under different working conditions. The simulation results of the mechanism with certain stability and accuracy are basically consistent with the experimental data and can be used to analyze the characteristics of 2-methylfuran-diesel combustion on diesel engines.