Interleukin-15 (IL-15) is an anabolic factor for skeletal muscle and several reports have described its important role as a regulator of energy homeostasis. In this study, we analyzed the effects of IL-15 on adipocyte differentiation using the 3T3-L1 preadipose cell line. The data show that IL-15 tends to reduce the rate of adipocyte proliferation, induces apoptosis, and partially stops differentiation. The signaling molecules behind these actions of the cytokine on adipose cells are: p42/p44 MAPK (which seem to be associated with the reduced rate of proliferation induced by the cytokine), STAT5 (which is related to the actions of IL-15 on differentiation), and SAPK/JNK (which are related to the increased apoptosis induced by IL-15). In conclusion, using the 3T3-L1 adipocyte cell line, the results presented here show that IL-15 exerts important effects on differentiation, proliferation and apoptosis. Altogether, the results presented here reinforce the idea that IL-15 is an important mediator that regulates adipose size and, therefore, the role of the cytokine in affecting body weight and obesity deserves additional studies.