Abstract: Multi-focus image fusion plays important roles in image recognition and analysis. In order to preserve the details of source images well and overcome artificial textures and non-uniform grayscale that is produced by lacking spatial continuity in transform domain fusion algorithms. A new multi-focus image fusion algorithm based on guided filtering via complex Contourlet domain is proposed. The new method holds the advantage of time-frequency separation of complex Contourlet and the feature of guided filtering. First, complex Contourlet is utilized for decomposition of the source images, and then apply average weight fusion rule with guided filtering to the low frequency coefficients of complex Contourlet, and apply larger sum-modified-Laplacian with guided filtering fusion rule to the high frequency coefficients of decomposition, finally the fusion image is reconstructed by the inverse complex Contourlet. The algorithm uses the guided filtering significantly enhance the transform domain fusion algorithms’ spatial continuity. Experimental results demonstrate that the proposed fusion method can both obtain good visual effect and highly objective.