The duodenum receives the hepatic and pancreatic ducts and is lined by a simple epithelium of columnar cells together with numerous goblet cells that produce mucus.

The surface area of the epithelium is greatly expanded by two structural features. Firstly, individual epithelial cells have a brush border facing into the lumen of the duodenum. The brush border forms a surface like a carpet with short bristles, but this is only just visible by light microscopy and is best seen by electron microscopy. Secondly, the epithelial surface area is expanded by large numbers of finger-like villi projecting into the lumen.

Villi are quite large structures (approximately 0.5 to 1 mm long and 0.2 mm thick) covered with columnar cells, and are seen here like fingers pointing towards the lumen of the small intestine towards the top of the window.

In the axis of each villus is a tubular lymph vessel called a lacteal.

The intestinal glands of Lieberkuhn are tightly packed glands with a simple tubular structure. Their main products are (1) mucus; (2) enzymes that attack peptides, fats and carbohydrates; and (3) enterokinase that activates trypsinogen from the pancreas to produce the digestive enzyme trypsin. The duodenal or Brunner's glands are tubuloalveolar glands (composed of tubes and thin walled vesicles) that produce mucus to protect the duodenal mucosa. In the intestinal wall are nodules or aggregations of lymphatic cells called Peyer's patches.