Image registration is the precondition and foundation in the fusion of multi-source image data. A two-step approach based on artificial immune system and chamfer matching to register images from different types of sensors is presented. In the first step, it extracts the large edges and takes chamfer distance between the input image and the reference image as similarity measure and uses artificial immune network algorithm to speed up the searching of the initial transformation parameters. In the second step, an area-based method is utilized to refine the initial transformation and enhance the registration accuracy. Experimental results show that the proposed approach is a promising method for registration of multi-sensor images.