ABSTRACT: The aim of this study was to identify genes, gene clusters and networks involved in sexual dimorphism and in the response to nutritional restriction in porcine skeletal muscles, through the analysis of gene expression differences. Full sib Iberian piglets from three litters composed of two males and two females per family were randomly assigned to two dietary treatments which differed in the feeding level during 15 wk. At the end of the trial, 27 wk of age, significant phenotypic differences were detected between genders and between feeding levels for growth, fatness, fatty acid composition and primary cuts weights. RNA samples from two skeletal muscles, diaphragm and Psoas major, were hybridized with Affymetrix microarrays and the expression data were analyzed using a mixed model and a FDR<0.01. The successfully performed validations by qRT-PCR of six selected genes supported the reliability of our microarray results. Ina a first step, the main gene expression differences between both muscles were established, identifying 181 differentially expressed genes, which represented almost exclusively anatomical structural differences. The analysis between genders reported expression differences of 59 unique genes, mainly implicated in muscle growth and stress response, including well known genes, such as IGF1, apart from others potentially associated to meat quality such as ANKRD1. The analysis of the feeding level effect restriction reported up-regulation of 76 genes and down-regulation of other 60 genes. Functional annotation showed that the moderated nutritional restriction applied led to a reduced growth through down-regulation of key genes implicated in enhancing growth and up-regulation of genes implicated in inhibiting growth. Besides, the restriction led to an increase of muscular aminoacid metabolism and decrease of lipid metabolism as adaptive response. Changes in expression patterns of genes determining meat characteristics, such as PDK4 implicated in water holding, CTSD associated to muscle transformation during meat processing and SCD involved in the determination of fatty acids profiles, were also reported. Finally, we identify relevant expression differences in ADAM12, CA2, UCHL1 and ESRRG genes, which are involved in human obesity and have not been previously studied in pig.