2-methyltetrahydrofuran (MTHF2) has been recently regarded as a promising alternative engine fuel. However, the chemical reaction mechanism for MTHF2 combustion in the engine has not been reported to date. In this study, a reduced diesel/MTHF2 reaction mechanism with only 78 species among 233 reactions was constructed for diesel/MTHF2 dual-fuel engine simulations. Firstly, a diesel surrogate mechanism involving the sub-mechanisms of n-decane, iso-octane, methylcyclohexane (MCH), toluene, a reduced mechanism of C2-C3 species and a detailed mechanism of H2/CO/C1 was selected. Secondly, a skeletal MTHF2 mechanism containing 54 species and 294 reactions was formulated under engine-relevant conditions using combined mechanism reduction methods. Thirdly, a reduced sub-mechanism of MTHF2 oxidation with 11 species and 13 reactions was extracted and combined with the four-component diesel surrogate fuel mechanism. Subsequently, the reduced diesel/MTHF2 mechanism was obtained by improving the combined five-component mechanism based on sensitivity analysis. Finally, the proposed mechanism was validated with selected experimental data of ignition delay times, flame species concentrations and laminar flame speeds. In addition, the new measurements from diesel/MTHF2 dual-fuel engine combustion were obtained and then utilized to further assess the developed mechanism. Overall, the developed diesel/MTHF2 mechanism can be used for diesel and MTHF2 dual-fuel engine combustion simulation.