Background/Aims: Animal models are valuable for studying pathogenic factors and preventive measures for colon anastomotic leakage. The suitability of the species as models varies greatly; however, no consensus exists on which species to use. The aim of this review was to evaluate different experimental animals for the study of clinical colon anastomotic leakage. Methods: PubMed and REX database were searched up to October 2010 to identify studies evaluating clinical colon anastomotic leakage in animal models and textbooks on experimental animals, respectively. Results: Functional models of clinical colon anastomotic leakage have been developed in the mouse, pig, rat, dog and rabbit. However, extreme interventions are needed in order to produce clinical leakage in the rat. Conclusion: Despite the wide use of the rat in this field of research, it seems that its resistance to intra-abdominal infection makes clinical leakage difficult to produce thus rendering the rat unsuited as a model. On the basis of the available literature, we recommend using mice as models mimicking clinical colon anastomotic leakage. Pigs may be an alternative; however, the existing models in this animal are less validated and clinically relevant.