The effects of three structural parameters on flow field and power consumption of in-line high shear mixer (HSM) were investigated by large eddy simulation (LES). In addition, an artificial neural network (ANN) is used to predict the relationship between the structural parameters and the power consumption, and the effect of dimensionless structural parameters on the power number constant Poz and k1 is studied. The results show that the stator tooth thickness and the tooth tip-base distance have a slight effect on the flow field, and the shear gap width is a key parameter affecting the flow field. As the stator teeth thickness, the tooth tip-base distance and the shearing gap width increases, the power number Po decreases. There is a linear relationship between the constant k1 and the dimensionless structural parameters. With the increase of the dimensionless parameter Ts/Ds-o of the stator tooth thickness, the dimensionless parameter St/H of the tooth tip-base distance, and the dimensionless parameter Sg/DR-o of the shear gap width, the constant k1 decreases. With the increase of the parameter St/H, Sg/DR-o and Ts/Ds-o, the constant Poz first increases and then decreases. There is a linear relationship between the constant Poz and the parameter Ts/h. With the increase of the parameter Ts/h, the constant Poz increases.