Sepsis is a systemic inflammatory response syndrome caused by infection, which has a complex mechanism. The gastrointestinal tract is commonly the first organ affected by sepsis, but intestinal disease itself can also induce sepsis. Roflumilast has been found to exert anti-inflammatory effects and, thus, the present study sought to examine its effect on intestinal damage caused by sepsis. In vivo studies were conducted using cecal ligation and puncture rat models, and in vitro experiments were performed using IEC-6 cells. The intestinal cells were first induced with lipopolysaccharide and the induced cells were then treated with roflumilast to evaluate its effects on phosphodiesterase (PDE)4 expression, intestinal function indices, release of inflammatory factors and cell apoptosis. The expression level of PDE4 in the small intestinal tissue of septic rats was found to be significantly higher compared with that in the normal group, suggesting that PDE4 may play a key role in intestinal injury caused by sepsis. It was found that roflumilast reduced PDE4 expression, as well as the levels of intestinal function indices, including lactate dehydrogenase, diamino oxidase and intestinal fatty acid-binding protein, in intestinal cells. Moreover, roflumilast reduced cellular damage, the release of inflammatory factors and apoptosis. In summary, the findings of the present study indicated that roflumilast can relieve the inflammation and apoptosis of intestinal cells caused by sepsis and can promote their functional recovery. These findings may promote the expansion of the clinical application of roflumilast in the future.