Abstract: Active Demons algorithm based on fractional differential has been proved to be effective for non-rigid image registration, and can solve the problem of low accuracy and low efficiency in image registration for intensity uniformity or weak texture region. However, the optimal order of fractional differential operator in the algorithm needs to be selected manually by multiple experiments, lack of order adaptive in image registration. Aiming at the problem, this paper proposes a new Active Demons algorithm based on multi-resolution and adaptive fractional differential. Firstly, an adaptive fractional order mathematical model is constructed based on the gradient magnitude and information entropy of image, therefore the optimal order and differential dynamic template are adjusted adaptively. Additionally, multi-resolution strategy is introduced to adaptive fractional differential Active Demons algorithm, therefore the registration efficiency is improved. Theory analysis and experimental results show that the proposed algorithm is capable of registrating images with intensity uniformity, weak edge and weak texture. And the optimal order of fractional differential operator can be calculated adaptively. Furthermore, the presented method can avoid falling into local optimum, thus the accuracy and efficiency of registration can be improved.