Absorption of food molecules is the major requirement for life. In the intestinal villus, absorption is a complex cellular process supported by the microvasculature and lymphatic system. During absorption of glucose, amino acids, and lipids, the villus interstitium develops a gradient of osmolarity from the base to the apex in the range of 450 to over 600 mOsm. Even at rest, the villus apex is more hypertonic and has a lower oxygen tension than at the base. Villus hyperosmolarity has implications for regulation of intestinal blood flow during food absorption. Data I obtained indicate the environment around major resistance arterioles of the submucosa becomes hypertonic due to the passage of hypertonic lymph and venular blood from the mucosal tissue. Perfusion of the lymph vessels with hypertonic media causes sustained dilation of the submucosal arterioles and about half of the dilation is linked to a sodium induced release of endothelial derived relaxing factor. The large arterioles and small arteries of the small intestine are proposed to be the dominant vessels responsible for decreased resistance and increased blood flow during absorptive hyperemia. The mechanism of dilation for large arterioles is primarily related to sodium induced hyperosmolarity caused by return of hypertonic blood and lymph from the mucosa and this can be tested by duplication of same sodium hyperosmolarity as occurs beside each arteriole during glucose or oleic acid absorption. The processes of counter-current exchange of oxygen and simultaneous counter-current exchange and multiplication of absorbed materials have been proposed to explain the origin of the intestinal hyperosmolarity and the higher oxygen tension in the villus base than apex. However, a much simpler explanation is possible. The fundamental cellular mechanism which establishes the gradient of osmolarity and oxygen tension from the villus apex to base may be greater sodium ion absorption at rest and cellular co-transport of amino acids and glucose with sodium molecules in the apical than basal portions of the villus. The hypertonic interstitial fluid produced in the villus apex is moved by the flow of lymph from the villus apex to base in the lacteal system. The osmolarity at the villus base and submucosal layer is raised by equilibration with the more hypertonic lymph from the villus apex. The flow of lymph keeps the osmotic gradient from villus apex to base smaller than would expected due to the proposed major differences in absorptive rates along the villus shaft both at rest and during nutrient absorption. The greater absorption rate of sodium at rest and sodium with carbohydrates or amino acids in the apical than basal portions of the villus is potentially responsible for the reduction in oxygen tension from villus base to apex, rather than counter-current oxygen exchange in the villus. However, counter-current exchange of oxygen between arterioles and venules in the submucosa is likely because pilot studies indicate the percent saturation of hemoglobin is 15-25% in small venules compared to 40-60% in large venules. The efficiency of counter-current exchange of oxygen should be diminished as blood flow increases, which would reduce oxygen loss from the arterioles preceding the villus tissue. The overall hypothesis is that hyperosmolarity generated in the mucosa during nutrient absorption is a signal for dilation of the resistance vessels and oxygen delivery to the mucosa is improved by increased oxygen content of arteriolar blood due to decreased counter-current exchange of oxygen.