Abstract: Tongue coating (TC) is a layer of coating on the surface of the tongue dorsal mucosa, and observing its variable color and property is an important content of tongue diagnosis in traditional Chinese medicine (TCM). A large amount of existing evidence has showed that TC images and its material composition have important diagnostic value for systemic diseases, which constructs the modern scientific foundation for the scientific connotation of observing TC to assist clinical syndrome differentiation, prescription, and medication. However, it is still wanting in-depth exploration on the cellular and molecular biological mechanisms underlying TC formation. The current review systematically summarizes the main research literatures, proposes the potential regulatory mechanism of the immuno-neuro-endocrine system, biological toxins, and physical factors in the development of tongue coating, and draws upon innovative approach to exploring the biological mechanism of TC microenvironment including microorganisms, immunity, endocrine, mechanical stretching, temperature, etc. These advances provide valuable research ideas and technical platform for in-depth exploration on the biological mechanisms of TC variety, and promote the scientific research and clinical application of tongue diagnosis.