New Findings: What is the central question of this study? Does stress sensitivity and susceptibility to inflammation innate to certain rat strains make them vulnerable to bowel dysfunction? What is the main finding and its importance? Of four different rat strains, the Lewis rat, which displays both susceptibility to gastrointestinal inflammation and sensitivity to stress, exhibits the most aberrant gastrointestinal morphology and visceral pain sensitivity. Given the similarities to human functional bowel disorders, such as irritable bowel syndrome, this may make it a good model of this disease. Irritable bowel syndrome is a common, debilitating gastrointestinal (GI) disorder characterized by episodic exacerbations of symptoms such as abdominal pain, bloating and altered bowel habit. Contributory factors for the development of irritable bowel syndrome include genetics, childhood trauma and prior GI infection leading to chronic low-grade inflammation or immune activation. Additional considerations in comprehending the chronic relapsing pattern that typifies irritable bowel syndrome symptoms are the effects of both psychosocial and infection-related stresses. Background stress and immune profiles can influence gut permeability and visceral pain sensitivity. This study examined whether innate susceptibility to inflammation and stress sensitivity in four rat strains is associated with bowel dysfunction. The pain threshold to colorectal distension was assessed in Lewis, Fischer (F344) and spontaneously hypertensive rats and compared with Sprague-Dawley control animals. Colons were subsequently excised and morphologically assessed for total length, goblet cell hyperplasia and muscle and mucosal thickness. Lewis rats displayed visceral hypersensitivity compared with other strains. At a morphological level, the gastrointestinal tract from these rats displayed mucosal goblet cell hyperplasia and alterations in muscle layer thickness. The Lewis rat strain, which is reported to have increased susceptibility to GI inflammation in addition to stress sensitivity, had the most prominent features of physiological and morphological GI dysfunction. These data support the hypothesis that background strain is a key factor in the development and exacerbation of bowel dysfunction in rodent models.