Raltegravir (RAL) has been shown to be virologically effective in both treatment naive and triple class resistant patients. A more favourable metabolic profile associated with RAL in comparison with other antiretroviral drugs has also been observed. The aim of this study was to investigate the molecular mechanisms that could explain the lack of toxicity of this drug in metabolism. Thus, the effects of RAL on adipogenesis and adipocyte metabolism were analyzed using 3T3-L1 cells, a very adequate and convenient cell culture model for the investigation of adipose differentiation and metabolism. The effects of RAL on adipogenesis were evaluated by the Oil Red O staining after 8 days of induction of differentiation. Several adipogenic genes (C/EBP, PPAR, Pref-1 and AP2) were analyzed by real time PCR. Fully differentiated adipocytes were also incubated with RAL for 24 hours and glucose utilization, lactate production and glycerol release were analyzed. Thus, minimal effects of RAL on murine adipocyte differentiation were observed. Basal glucose uptake and lactate production were not affected by RAL at any of the concentrations used. No effects were also found on the percentage of glucose that is metabolized to lactate. Lipolysis was only slightly inhibited by Raltegravir (-10%) at the highest concentration used (50 µM), while no effects were observed with lower doses. Our results suggest that the absence of significant actions of RAL on adipogenesis and glucose and lipid metabolism in adipocytes could explain, at least in part, the neutral metabolic effects of RAL in clinical studies.