The aim of the paper is the comparison of the injection process with different fuels, i.e. a standard diesel fuel and a pure biodiesel. Multiphase cavitating flows inside diesel nozzles are analyzed by means of unsteady CFD simulations using a two-fluid approach with consideration of bubble dynamics, on moving grids from needle opening to closure. Two five-hole nozzles with cylindrical and conical holes are studied and their behaviors are discussed taking into account the different properties of the two fuels. Extent of cavitation regions is not much affected by the fuel type. Biodiesel leads to significantly higher mass flow only if the nozzle design induces significant cavitation which extends up to the outlet section and if the injector needle is at high lift. If the internal hole shaping is able to suppress cavitation, the stabilized mass flows are very similar with both fuels. On the contrary, as long as the lifts are small and the flow is turbulent, diesel fuel gives higher mass flows due to lower frictions along the needle seat and the nozzle walls. Detailed analyses of the injection processes are presented, including flow pattern development inside the nozzles.