We examined the impact of chronic stress on rat growth rate and intestinal epithelial physiology and the role of mast cells in these responses. Mast cell-deficient (Ws/Ws) rats and +/+ littermate controls were submitted to water avoidance stress or sham stress, 1 h/day, for 5 days. Seven hours after the last sham or stress session, jejunal segments were mounted in Ussing chambers, in which secretion and permeability were measured. Body weight (as a growth index) and food intake were determined daily. Stress increased baseline jejunal epithelial ion secretion (indicated by short-circuit current), ionic permeability (conductance), and macromolecular permeability (horseradish peroxidase flux) in +/+ rats, but not in Ws/Ws rats, compared with nonstressed controls. Stress induced weight loss and reduced food intake similarly in the groups. In +/+ rats, these parameters remained altered 24–72 h after the cessation of stress. Modulation of stress-induced mucosal mast cell activation may help in the management of certain intestinal conditions involving epithelial pathophysiology.