A two-step simulation methodology was applied for the computation of the injector nozzle internal flow and the spray evolution in diesel engine-like conditions. In the first step, the multiphase cavitating flow inside injector nozzle is calculated by means of unsteady CFD simulation on moving grids from needle opening to closure. A non-homogeneous Eulerian multi-fluid approach - with three phases i.e. liquid, vapor and air - has been applied. Afterward, in the second step, transient data of spatial distributions of velocity, turbulent kinetic energy, dissipation rate, void fraction and many other relevant properties at the nozzle exit were extracted and used for the subsequent Lagrangian spray calculation. A primary break-up model, which makes use of the transferred data, is used to initialize droplet properties within the hole area.The paper focuses on the analysis of the injection process comparing the effects different fuels - a standard diesel fuel and a pure biodiesel, methyl ester of soybean oil - in two types of nozzles, i.e. cavitating and non-cavitating.Biodiesel fuel is characterized by higher density, higher viscosity and lower vapor pressure, compared to diesel fuel. Extent of cavitation region was found to be strongly dependent on the nozzle shape, whereas not much affected by the fuel type. Detailed analyses of the injection processes are presented, including flow pattern development inside the nozzles. Simulations of the spray evolution are also discussed highlighting the differences between the use of fossil and biodiesel fuels in terms of spray penetration, atomization and spray angle. Simulations of spray evolutions, in non-evaporative conditions, highlighted that hole shape affects diesel penetration and angle. Biodiesel spray, instead, is less sensitive to hole shaping. SMD is larger for biodiesel, irrespectively of hole shape and injection pressure. Diesel fuel in non-cavitating nozzle provides higher penetration and lower spray angle.