Introduction: Maternal obesity can induce an excess of fatty acid transfer to the fetus, which could alter the physiology of fetal skeletal muscle. These effects could be reverted by a supplementation with docosahexaenoic acid (DHA). In adult muscle fiber, obesity leads to elevated intramuscular lipid content that activate NOX2, by the forming of an active complex between gp91phox, sarcolemma subunit with p47phox (cytosolic subunit), stimulating the lipoperoxidation and disrupting the insulin signaling. In turn, perilipin 5 (PLIN5), a lipid droplet-binding protein act as a protective factor against lipotoxicity. Therefore, we aimed to test, in a mouse model of maternal obesity, if maternal obesity stimulates a higher expression of gp91phox , p47phox and activates NOX2 in fetal muscle, which could be prevented by the stimulation of PLIN5 expression induced by the supplementation with DHA. Methods: A total of 24 C57BL/6J female mice were fed with a control diet (CON; 14% Kcal of fat) or high fat diet (OB; 45% Kcal of fat) five weeks, mated and maintained with the same diet during gestation. Since gestational day (GD) 6.5 until GD 16.5, a subgroup of CON and OB were supplemented with DHA (50 mg/kg of body weight). At GD 17.5, dams were euthanatized, and fetus were collected and weighed. Legs from two fetus of each litter were obtained in order to isolate the tissues for studying the expression of PLIN5, gp91 and p47 using western blot. Assembly of gp91phox and p47phox was assessed by indirect immunofluorescence in isolated myoblast after 5 days of culture. Differences were evaluated by ANOVA one way following Tukey test. A p-value < 0.05 was considered as significant. Results: Our preliminary data shows that the assembly of gp91phox and p47phox subunits of NOX2 is present in the sarcolemma of fetal muscle in the offspring of obese dams. We found a higher expression of gp91phox in fetuses from OB dams compared to fetuses from CON (P = 0.049). In turn, PLIN5 showed tended to be higher in OB compared to CON, whereas DHA supplementation induced a higher expression of PLIN5 in CON+DHA and OB+DHA compared to CON and OB groups, respectively. Conclusion: The assembly of NOX2 subunits suggests that fetal muscle is susceptible of lipoperoxidation mediated by this enzyme. It seems that gestational obesity upregulates gp91, and then activate the NOX2. DHA seems to be a stimulator of PLIN5, forming part of the lipid droplets and acting as a protection from lipid oxidation and oxidative stress in muscle of fetal mice.