Abstract: Compositions and formulations useful for treating inflammatory bowel diseases, intestinal cancers, and improving the integrity of the luminal surface of the gastrointestinal tract are disclosed. Typically, the composition increases level of cGMP in the intestinal mucosa or increases the activity of a PKG, preferably PKG2, in the intestinal mucosa. Preferably, the composition includes a phosphodiesterase type 5 (PDE5) inhibitor and is targeted to the intestinal mucosa, for example by enteric coating or attachment of an intestinal specific targeting moiety. Methods of using the compositions to treat intestinal and bowel diseases, and intestinal cancers, and methods of improving one or more physiological parameters of intestinal luminal integrity including, but are not limited to, reduced proliferation for example in the intestinal crypts, reduced apoptosis for example at the luminal surface, and induction of downstream effectors of PKG-mediated signaling are also disclosed.