Zinc is known to be an essential trace metal which is necessary for health and growth, and is also essential for the function and activity of over 200 metalloenzymes. A relationship between zinc and obesity was first found in obese patients and obese mice (genetically and dietary obese) to that the obese had lower blood zinc levels than their lean controls, and the zinc level was inversely related to the degree of obesity. The therapeutic effect of zinc on obesity is still a controversial subject. This study was to investigate the alterations of tissues zinc distribution, dietary zinc effect in obese mice, and the interactive combinations of zinc and endocrine factors in obese patients. Zinc and body fat contents were determined by atomic absorption spectrometer and gravimetrically, respectively. The results indicated that dietary zinc treatment increased body fat deposition in obese mice. Obese mice carried markedly low zinc levels in most of the peripheral tissues, but retained a great amount of zinc in liver and adipose tissues compared with lean mice. Clinically, zinc was found to be correlated with thyroid hormone conversion and insulin resistance. Although the true metabolic role of zinc in obesity is still obscure, the relationships between zinc, endocrine factors, and neurotransmitters, and interactions with other trace metals are needed to throw light on the subject. These approaches to thermoregulation and metabolic mechanisms of obesity and diabetes mellitus may be of great interest in the future.