Abstract: The sovlving methods of depletion equation is researched, including Taylor method,Pade method, Scaling and squaring method（Scale）, Eigenvectors method（Eig）, Chebyshev rational approximation method（Cram）, Lagrange interpolation method, Newton interpolation method,Vandermonde method and Krylov subspace method. Based on the comparison and analysis of accuracy and efficiency, Cram is chosen as the candidate for the final depletion method. The program of solving depletion equation is developed and validated with burnup benchmark. Results show that the program developed can provide accurate solution.