Mental or emotional stress has been shown to cause mast cell degranulation in several different tissues. Several lines of experimental evidence indicate that stress, working through the sympathetic nervous system, or the hypothalamus-pituitary-adrenal axis, stimulates peripheral nerves to release neuropeptides that bind to receptors on the mast cells, causing them to degranulate. In order to investigate the effects of stress on mast cell degranulation, it is necessary to first establish a reproducible animal model of stress (in this case, rat) and also to ensure that the control animals do not show any signs of stress. This procedure requires a great deal of care and attention because the methods used by many institutions to house laboratory rodents, do in fact cause them stress. This topic is addressed in this chapter. In addition, two histological techniques are described to visualize connective tissue and mucosal mast cells and to assess their degree of degranulation.