Molecular dynamics simulation is performed to investigate the wetting behaviors of Pb droplet on Ni(100), Ni(110) and Ni(111) substrates. It has been shown that the wetting behavior of precursor film is isotropic for Pb droplet on Ni(100) and Ni(111) substrates, but anisotropic for Pb droplet on Ni(110) substrate. The demonstrated anisotropy is attributed to the differences in diffusion mechanism and rate along different crystal orientations for Pb atoms with corresponding anisotropic structure of the crystal lattice on Ni(110) substrate. The spreading dynamics of precursor film on different lattice surfaces are also investigated, which shows that there is no surface alloy formed for Pb droplet on Ni(111) surface and the spreading dynamics can be described by R2 t, but surface alloy forms for Pb droplet on Ni(100) and Ni(110) surface and the spreading dynamics satisfies R4 t, at the same time the spreading rate of droplet on Ni(100) is higher than that of Ni(110) substrate.