Apelin, the endogenous ligand of the APJ receptor, has been identified in a variety of tissues, including stomach, heart, skeletal muscle, and white adipose tissue (WAT). We sought to clarify the effects of apelin on body adiposity and the expression of uncoupling proteins (UCPs) in C57Bl/6 mice. Treatment with intraperitoneal (ip) apelin at a dose of 0.1 µmol/kg/day for 14 days decreased the weight of WAT, serum levels of insulin and triglycerides compared to controls, without influencing food intake. Apelin treatment also decreased body adiposity, serum levels of insulin and triglycerides in obese mice fed a high-fat diet. Apelin increased the serum adiponectin level and decreased that of leptin. Additionally, apelin treatment increased mRNA expression of UCP1, a marker of peripheral energy expenditure, in brown adipose tissue (BAT) and of UCP3, a regulator of fatty acid export, in skeletal muscle (MSL). In addition, immunoblot bands and relative densities of UCP1 content in BAT were also higher in the apelin group than in controls. Furthermore, apelin treatment increased body temperature and O₂ consumption and decreased the respiratory quotient. In conclusion, apelin appears to regulate adiposity and lipid metabolism both in lean and obese mice. In addition, apelin regulates insulin resistance by influencing the circulating adiponectin level, the expression of BAT UCP1, and energy expenditure in mice.