The Aim of this study is to determine the histological structure in the wall layers of large intestine of guinea pig. The cecum and colon was characterized by a delicate lining that is moisturized by mucus and also by a gel that is a by-product of bacterial fermentation. This study was performed on the cecum and ascending and descending colon in five health animals. The cecum and colon wall was composed of four tunicae (mucosa, submucosa, muscularis and serosa, the tunica mucosa consist of epithelium, lamina propria and muscularis mucosa. The colon lumen lined by simple columnar epithelium with prominent goblet cells. The epithelial surface of the colon is covered by the openings of tubular intestinal glands which penetrate deep into the thick mucosa. The glands consist of absorptive cells that absorb water and salt, goblet cells were secrete the mucus, and scattered Paneth cells. Crypts of Lie beckon (intestinal glands) are a simple tubular glands is observe in most mammals, which extending from the muscularis mucosa through the thickness of the lamina propria and they open into the intestinal lumen. Muscularis mucosa, consisted of very thin two layers of inner circular and outer longitudinal smooth muscles, the greater thickness of the muscularis mucosa was in the adult type and the submucosa was consists of dense a irregular connective tissue. The muscular layer is consists of internal circular and external longitudinal layers of smooth muscles, which mean their thickness is decreased toward the last parts. Thus, the serous coat is a thin layer of loose connective tissue, the thickness was decreases toward the last parts.