Obesity has become a global public health problem associated with complications including type 2 diabetes, cardiovascular disease, and several cancers. Adipocyte differentiation (adipogenesis) plays an important role in obesity and energy homeostasis. Adipose tissue secretes multiple cytokines and adipokines which can cause the complications of obesity, especially insulin resistance. TNF-α, IL-6, leptin, and resistin have been identified as the main regulators of obesity and insulin activity. miR-378 is highly induced during adipogenesis and has been reported to be positively regulated in adipogenesis. In the current study, matured human adipocytes were treated with TNF-α, IL-6, leptin, or resistin on the 15th day after the induction of human pre-adipocyte differentiation. We demonstrated that TNF-α, IL-6, and leptin upregulated miR-378 expression indicating that miR-378 probably is a novel mediator in the development of insulin resistance related to obesity.