Hepatic uptake of insulin by the in situ perfused rat liver has been measured in rats subjected for 9 wk to physical training (T rats) on a treadmill. Three sedentary groups, one food-restricted (FR) to have the same weight as T rats, one freely-eating (FE), and one sucrose-fed (SF) were also studied. Each liver was cyclically perfused for 30 min with three different insulin concentrations in the medium (approximately 80, approximately 500, and approximately 2000 microunits/ml). Plasma insulin concentrations in T rats were 50 and 17, in FR 55 and 20, in FE 71 and 30 and in SF 84 and 42 microunits/ml in portal and peripheral venous plasma, respectively. Insulin decay curves followed first order kinetics. Taking FE rats as controls physical training enhanced hepatic clearance (expressed in ml/g/min) by 37%-60% whereas sucrose feeding reduced it by 15%-31% during the three perfusion periods. Food restriction in the FR rats caused only minor changes. Similar results were obtained with respect to hepatic extraction ratio and insulin removal. There was a significant negative correlation between portal insulin concentration and hepatic clearance rate. The results indicate that the hepatic extraction of insulin depends on portal insulin concentration. The mean net insulin uptake of the liver was similar in the groups, utilizing portal insulin concentrations and the hepatic clearance rate for calculations. As previously shown, the low peripheral plasma insulin levels after physical training are due mainly to a decreased insulin secretion from the pancreas. This is thus magnified by the efficient trapping of insulin in the liver.