As new regulators at the post-transcriptional level, microRNAs (miRNAs) are non-coding 19-22 nucleotide RNA molecules that are believed to regulate the expression of thousands of genes. Since the monounsaturated fatty acid oleate can reverse insulin resistance induced by the saturated fatty acid palmitate, we carried out microarray analysis to determine differences in miRNA expression profiles in mouse muscle C2C12 cells that were treated with palmitate and palmitate plus oleate. Among the altered miRNAs, the expression levels of miR-7a, miR-194, miR-337-3p, miR-361, miR-466i, miR-706 and miR-711 were up- or down-regulated by palmitate, but restored to their original level by oleate. These results were verified by quantitative RT-PCR (QRT-PCR). Further studies showed that over-expression of miR-7 down-regulated insulin receptor substrate 1 (IRS1) expression as well as inhibited insulin-stimulated Akt phosphorylation and glucose uptake. The miRNA expression profiles correlated to oleate protection against palmitate-induced insulin resistance in mouse muscle cells offer an alternative understanding of the molecular mechanism of insulin resistance.