Selective permeability for small proteins and oligopeptides occurs in the intestinal epithelium of many animal species and humans. Whole proteins are sometimes endocytosed and undergo partial hydrolysis in intestinal epithelial cells with the probable release of essential oligopeptides into the bloodstream. Increased permeability to certain proteins can cause asthma and other metabolic disorders. Permeable proteins have also been successfully used to deliver vaccines or drugs via oral consumption. Protein absorption has been inferred in many cases and demonstrated in some cases by histochemical, tracer, and analytical techniques. However, the nature and importance of protein absorption remains largely unknown. Here, we demonstrate the movement of two lumenal proteins (GFP: 26 kDa and OFP: 23 kDa) across the intestinal epithelium of fish and mice using laser scanning confocal microscopy. The results provide evidence that small proteins can be taken up intact by intestinal epithelial cells, even though large proteins are digested to single amino acids or protein fragments before they are absorbed. Our results suggest that it is possible to orally administer some small proteinous medicines for therapeutic purposes.