The water buffalo represents an important source of animal products in Egypt and characterized by high resistance to several diseases and parasites. The present study carried out on the Egyptian water buffaloes of different ages (from 50 days to 8 years old buffaloes) to illustrate the structure of ileal Payer's patches with age. The specimens of ileum were fixed and processed for light and electrone microscopy The Payer's patches (PPs) formed of elongated dome regions flanked by intestinal villi. These domes were short, wide villi. The domes were consisted of lymphoid follicles covered with a typical dome- associated epithelium of enterocytes and M cells without any goblet cells in young and adult ages. The M cells showed variable appearance depending on the functional status. The lymphoid follicles had a clear germinal center. In conclusion Payer's patches (PPs) were still active until the age of 5 years old and then begin to be inactive at 8 years old we think there is a long period of activity which express the tolerance to many diseases.