Bioluminescence imaging is a recent modality to visualize biological effects, especially for small animals. However, the acquired images are degraded by diffusion and absorption phenomena from the tissue and by the acquisition system itself. In this paper, we use restoration methods to enhance the quality of bioluminescence images. We propose a model for image formation and an experimental determination of the PSF (Point Spread Function). Several restoration methods are compared on test images generated according to the model and on real data. This comparison is insured by using MSE (Mean Square Error) and two other quantitative criteria. Results showed that the statistical methods give more accurate restoration and are well adapted for Bioluminescence Imaging. © 2008 Springer-Verlag.