Anti-adipocyte monoclonal antibody has been shown to reduce body fat mass in animals. Here, we investigated the effects of an anti-adipocyte antibody (single-chain variable fragment and crystallizable fragment, scFv-Fc) on pig subcutaneous adipose tissue development and lipid metabolism. The scFv-Fc antibody did not alter feed intake or body weight of treated pigs. It suppressed subcutaneous adipose tissue development by reducing the percentage of larger adipocytes, which led to a reduction in body fat mass and subcutaneous adipose tissue thickness. Body fat mass was reduced by reducing triglyceride biosynthesis and promoting triglyceride lipolysis in adipose tissue. There was an increase in lipoprotein lipase mRNA expression in adipose tissue and activity in blood and an enhanced transportation of circulating high-density lipoprotein, low-density lipoprotein, and free fatty acids. Blood concentrations of triglyceride, total cholesterol, glucose, insulin, and adiponectin and mRNA expression of adiponectin in adipose tissue remained unaffected. These findings suggest that anti-adipocyte scFv-Fc antibody may have an application for reducing body fat mass in obese subjects.