Background/Aims: In chronic renal failure (CRF), zinc deficiency is partially attributed to decreased intestinal zinc absorption, but the mechanism of this decrease in intestinal zinc absorption is obscure. Therefore, the objective of this study was to investigate the cause of decreased intestinal zinc absorption in a uremic rat model using an in vivo perfusion technique as well as to evaluate the effect of intestinal zinc perfusion on the secretion of biliary zinc in normal and CRF rats. Methods: CRF was induced by five-sixths nephrectomy (Nx). During zinc sulfate perfusion, absorption of zinc in the small intestine and the response of plasma zinc level were measured. After intestinal zinc perfusion for 80 min, the concentrations of zinc and metallothionein (MT) in the intestinal mucosal and liver tissue were assayed. The secretion of biliary zinc and the excretion of urinary zinc were also determined before and after zinc sulfate perfusion. The results were compared with those obtained from 10 sham-operated normal rats. Results: The CRF rats showed a significant decrease in the rate of intestinal zinc absorption and in the response of plasma zinc levels during intestinal zinc perfusion. They also had significantly higher levels of mucosal zinc and MT than sham-operated normal rats, but their contents of liver zinc were significantly lower than those of sham-operated normal rats after zinc sulfate perfusion. CRF rats showed a low plasma zinc level and a high urinary zinc excretion in baseline levels, but had similar output of basal biliary zinc as compared with sham-operated normal rats. Zinc sulfate perfusion in the small intestinal was not found to increase the secretion of biliary zinc and the excretion of urinary zinc, either in normal or CRF rats. Conclusion: In the CRF rat, the reduction of intestinal zinc absorption may result from reduced mucosal zinc efflux from the basolateral membrane into plasma. These data also suggest that the absorbed zinc from the gastrointestinal tract is mostly taken up by the liver or other tissues, and is less excreted in bile juice and urine.