Segmenting medical images is still a challenging task for both traditional local and global methods because the image intensity inhomogeneous. In this paper, two contributions are made: (i) on the one hand, a new hybrid model is proposed for medical image segmentation, which is built based on fractional order differentiation, level set description and curve evolution; and (ii) on the other hand, three popular definitions of Fourier-domain, Grünwald-Letnikov (G-L) and Riemann-Liouville (R-L) fractional order differentiation are investigated and compared through experimental results. Because of the merits of enhancing high frequency features of images and preserving low frequency features of images in a nonlinear manner by the fractional order differentiation definitions, one fractional order differentiation definition is used in our hybrid model to perform segmentation of inhomogeneous images. The proposed hybrid model also integrates fractional order differentiation, fractional order gradient magnitude and difference image information. The widely-used dice similarity coefficient metric is employed to evaluate quantitatively the segmentation results. Firstly, experimental results demonstrated that a slight difference exists among the three expressions of Fourier-domain, G-L, RL fractional order differentiation. This outcome supports our selection of one of the three definitions in our hybrid model. Secondly, further experiments were performed for comparison between our hybrid segmentation model and other existing segmentation models. A noticeable gain was seen by our hybrid model in segmenting intensity inhomogeneous images.