Hyaluronic acid, or hyaluronan (HA), is a nonsulfated glucosaminoglycan that has long been recognized for its hydrophilic properties and is widely used as a dermal filler. Despite much attention given to the study of other extracellular matrix (ECM) components, in the field of ECM properties and their contribution to tissue fibroinflammation, little is known of HA’s potential role in the extracellular milieu. However, recent studies suggest that it is involved in inflammatory response, diet-induced insulin resistance, adipogenesis, and autoimmunity in type 1 diabetes. Based on its unique physical property as a regulator of osmotic pressure, we emphasize underestimated implications in adipose tissue function, adipogenesis, and obesity-related dysfunction.