Abstract: On the basis of the MATLAB simulation platform and the grain nucleation and growth theory, the numerical calculation model of microstructure evolution of laser cladding layer of Inconel625 alloy was constructed by cellular antomata-finite difference method. The microstructure evolution of the alloy during single pass laser cladding was simulated by the model and verified by experiments. The effects of laser heat input and heterogeneous nucleation quantity on the grain morphology of the cladding layer were studied. The results show that according to the established model simulation, the inner part of the cladding layer was composed of columnar crystals and sub-grains distributed between columnar crystals, and the cladding layer near the fusion line consisted of cellular crystals; the simulation was consistent with the test results. The average size of columnar crystals obtained by simulation and test were 2.817, 2.743 μm, respectively, and the relative error was only 2.69%, which verified the reliability of the calculation model. With decreasing laser heat input or increasing heterogeneous nucleation quantity, the microstructure of the cladding layer was gradually refined, the number of grains increased, and the size of the columnar crystals decreased.