The absorption characteristics of etretinate were examined in the Sprague‐Dawley rat with the use of the in situ intestinal lumen perfusion model. Intestinal segments of 15–50cm were cannulated and perfused with etretinate solutions of 178–1405 μgml−1 in a single‐pass manner at flow rates of 0·15–0·96 ml min−1. The intestinal effluent was collected and analyzed by HPLC for etretinate, as was blood that was drawn from the jugular vein. Despite its lipophilic nature, etretinate does not appear to be well absorbed from the rat intestine; the maximum fraction disappearing from the intestinal lumen was approximately 0·35. The absorption of etretinate appeared to be controlled by the aqueous diffusion layer. There was no evidence that the uptake of etretinate by the gastrointestinal membrane involved an active transport system.