The enteric nervous system exerts local control on the gastrointestinal motility, exocrine and endocrine secretions, ensures proper blood supply, and modulates the immune and inflammatory processes in the gut. The aim of this paper is to give insights into current advances and present knowledge about morphology of the myenteric plexus and the neurochemical coding of adult rat myenteric neurons in the large intestine with a special emphasis on non-adrenergic, non-cholinergic (NANC) transmitters. Major neuroactive substances involved in the NANC transmission include nitric oxide (NO), tachykinins, mostly substance P (SP), and adenosine triphosphate (ATP), co-localized in variable proportions with other neuroactive substances. After applying NADPH-diaphorase enzyme histochemistry and neuronal NO synthase (nNOS) immunohistochemistry, we were able to demonstrate numerous nitrergic somata of myenteric neurons with Dogiel type I morphology. In addition to the observed nitrergic distributional patterns, significant variations were registered in the staining intensity of myenteric structures in the colon and anorectal area. Immunohistochemistry for SP revealed an abundance of intensely stained SP-immunoreactive varicose fibers, ensheathing the immunonegative myenteric neuronal cell bodies in a basket-like manner. ATPergic structures were mostly limited to fiber bundles surrounding unstained myenteric neurons and penetrating the two muscle layers. An important finding was the notable presence of purinergic immunoreactive nerve fiber bundles in the longitudinal muscle layer. In conclusion, our results show that the cytoarchitecture and morphometric properties appeared to mimic their equivalent in the more proximal parts of the rat digestive tract and in other experimental animals.