Abstract: To study the effect of microchannel inlet angle on the droplet generation process under the condition of varying fluid physical parameters, a three dimensional numerical simulation in the cross-flow microchannel was proposed by the volume of fluid (VOF) method. The two-phase pressure difference in the droplet generation process, the time period and size of the microdroplet were studied. The results show that the microdroplet size decreases firstly and then increases gradually with the increase of the inlet angle in the squeezing regime. A 90° inlet angle is helpful to generating shortest droplet for high surface tension or low viscosity of continuous phase; A 120° inlet angle is conducive to generating shortest droplet for low surface tension or high viscosity of continuous phase. For constant inlet angle, the microdroplet size rises with the increase of the surface tension coefficient and reduces with the increase of the viscosity of continuous phase. The shortest droplet is generated in different microchannel for varying fluid physical parameters. Considering the inlet angle, surface tension coefficient and viscosity of continuous phase, the new correlation of the dimensionless droplet length for the squeezing regime is proposed which can provide guidance for the design and application of the microdroplet system.