The pathophysiology of irritable bowel syndrome (IBS) is complex and not fully understood, so the aim of this study was to evaluate whether visceral and somatic hypersensitivity, autonomic cardiovascular dysfunction, and low-grade inflammation of the gut wall are associated with diarrhea-predominant IBS (D-IBS). Sixty-two patients with D-IBS and 20 control subjects participated in the study. Using the ascending method of limits (AML) protocol, we demonstrated that D-IBS patients had significantly lower sensory thresholds compared with healthy controls (P<0.001). Using diverse methods, especially the ischemic sensitivity test, for the first time in China, we confirmed that D-IBS patients have somatic hypersensitivity. They had a significantly higher systolic blood pressure and heart rate after a cold stimulus, indicative of autonomic cardiovascular dysfunction. Compared with the control group, D-IBS patients had a significantly higher level of calprotectin (P<0.001). We also found significant correlations between visceral and somatic hypersensitivity, visceral hypersensitivity and autonomic cardiovascular dysfunction, and somatic hypersensitivity and autonomic cardiovascular dysfunction. Our findings may provide valuable suggestions for the treatment of D-IBS.