Obesity is considered as an inflammatory disease, in which free radical-induced oxidative stress and excessive intake of macronutrients exacerbate their symptoms. In this context, we assessed in rats the possible preventive effect of the supplementation with an antioxidant molecule, ascorbic acid, in order to reduce the adiposity induced by the intake of a high-fat diet. For this purpose, during 56 days, three groups of male Wistar rats were fed on: a) standard pelleted diet, b) Cafeteria diet, c) ascorbate-supplemented (750 mg/kg of body weight) Cafeteria diet. At the end of the experimental period, microarray analysis was used to identify genes transcriptionally induced or repressed by both experimental dietary models (Cafeteria diet supplemented or not with ascorbic acid) in subcutaneous adipose tissue. Dietary ascorbic acid was able to protect against high fat diet effects, reducing the increase of body weight, total body fat and enlargement of different adipose depots induced by the Cafeteria diet without affecting food intake. An association analysis accurately and differentially allowed the detection of gene expression changes related with adiposity and insulin resistance. The genes that more strongly correlated with body fat and HOMA insulin resistance index were involved in adipocyte differentiation, lipid and glucocorticoid metabolism, cell cycle regulation, as well as in several insulin-induced processes. Some other transcripts are regulated by the vitamin C-mediated reduction of adiposity, such as genes that participate in glucocorticoid metabolism, adipogenesis, pentose phosphate pathway, or tricarboxylic acid cycle. This strategy was able to link variations in adipose tissue gene expression with markers of diet-induced obesity in rats, such as insulin resistance and body fat content.