Long non-coding RNAs (lncRNAs) are emerging as important regulators in the modulation of muscle development and muscle-related diseases. To explore potential regulators of muscle differentiation, we determined the expression profiles of lncRNAs and mRNAs in C2C12 mouse myoblast cell line using microarray analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to explore their function. We also constructed co-expression, cis/trans-regulation, and competing endogenous RNA (ceRNA) networks with bioinformatics methods. We found that 3067 lncRNAs and 3235 mRNAs were differentially regulated (fold change ≥2.0). Bioinformatics analysis indicated that the principal functions of the transcripts were related to muscle structure development and morphogenesis. Co-expression analysis showed 261 co-expression relationships between 233 lncRNAs and 10 mRNAs, and nine lncRNAs interacted with myog and MEF2C collectively. Cis/trans-regulation prediction revealed that lncRNA Myh6 could be a valuable gene via cis-regulation, and lncRNAs such as 2310043L19Ris, V00821, and AK139352 may participate in particular pathways regulated by transcription factors, including myog, myod1, and foxo1. The myog-specific ceRNA network covered 10 lncRNAs, 378 miRNAs, and 1960 edges. The upregulated lncRNAs Filip1, Myl1, and 2310043L19Rik may promote myog expression by acting as ceRNAs. Our results offer a new perspective on the modulation of lncRNAs in muscle differentiation.