In this study, we examine the responsiveness of intestinal epithelial cell turnover to leptin (LEP) in correlation with leptin receptor (LEPr) expression along the villus-crypt axis in a rat with short bowel syndrome (SBS). Adult rats underwent either a 75% intestinal resection or a transection. SBS-LEP rats underwent bowel resection and were treated with LEP starting from the fourth postoperative day. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined at sacrifice. RT-PCR technique was used to determine Bax and Bcl-2 gene expression in ileal mucosa. Villus tips, lateral villi, and crypts were separated using laser capture microdissection. LEPr expression for each compartment was assessed by quantitative real-time PCR (Taqman). Treatment with LEP significantly stimulated all parameters of adaptation. LEPr expression in crypts significantly increased in SBS rats (vs Sham rats) and was accompanied by a significant increase in enterocyte proliferation and decreased apoptosis after LEP administration. A significant increase in LEPr expression at the tip of the villus in SBS rats was accompanied by decreased cell apoptosis. In conclusion LEP accelerated enterocyte turnover and stimulated intestinal adaptation. The effect of LEP on enterocyte proliferation and enterocyte apoptosis correlated with receptor expression along the villus-crypt axis.