An intensity-based non-rigid registration algorithm is discussed, which uses Gaussian smoothing to constrain the transformation to be smooth, and thus preserves the topology of images. In view of the insufficiency of the uniform Gaussian filtering of the deformation field, an automatic and accurate non-rigid image registration method based on B-splines approximation is proposed. The regularization strategy is adopted by using multi-level B-splines approximation to regularize the dis-placement fields in a coarse-to-fine manner. Moreover, it assigns the different weights to the estimated displacements according to their reliabilities. In this way, the level of regularity can be adapted locally. Experiments were performed on both synthetic and real medical images of brain, and the results show that the proposed method improves the registration accuracy and robustness.