The mucosal immune system is at the forefront of defense against invading pathogens but, at the same time, must maintain tolerance toward commensals and food antigens in the intestinal lumen. The interplay between the innate immune response and commensal micro organisms is essential in this process. Great progress has been made to identify some of the genetic predispositions underlying inflammatory bowel disease (IBD) in certain breeds, such as the German Shepherd Dog. Some immunological markers, such as cytokine measurement, immunohistochemistry for p-glycoprotein expression, perinuclear anti-neutrophil cytoplasmic antibodies and PCR for antigen receptor rearrangement, are discussed for their clinical usefulness in the diagnosis and management of IBD.