The mechanism of NOx and soot reduction using different pilot and multiple injection strategies has been computationally studied in a heavy duty DI Diesel engine. A designed set of advanced injection schemes with various variables and exhaust gas recirculation rate (up to 10%) have been analyzed. The CFD model was firstly calibrated against experimental data for a part load operation at 1600 rpm. The computational models used were found to predict the correct trends obtained in the experiment. The study demonstrated the potential and explained the mechanism of the combination of EGR and multiple injection to reduce both soot and NOx emissions together with improved fuel economy. The results showed that injecting a small percentage of fuel in the pilot injection pulse (e.g., 5%) accompanied with adequate fuel in the second injection pulse (e.g., 25%) can reduce the ignition delay and the premixed combustion period, leading to lower temperature and NOx emission while not increasing soot formation in the late combustion phase. It has been also found that increase the number of injection pulses (up to five separate injection pulses per engine cycle) can be more beneficial for the reduction of NOx and soot emissions compared with split injection cases, however the amount of BSFC in these cases should be considered as a main disadvantage.