This study aimed to explore the underlying molecular mechanisms of idiopathic Parkinson's disease (IPD) by bioinformatics analysis. Gene expression profile GSE34516 was downloaded from the Gene Expression Omnibus. Eight locus coeruleus post-mortem tissue samples derived from four IPD patients and four neurological healthy controls were used to identify the differentially expressed genes (DEGs) by paired t test. Based on the DEGs, principal components were analyzed. The Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway analysis of the genome microarray data were then performed. Finally, protein-protein interaction (PPI) network of the DEGs was constructed. Total 261 DEGs including 195 up-regulated and 66 down-regulated DEGs were identified. Intracellular protein transport and RNA splicing via transesterification reactions were selected as the most two significantly enriched functions. Mismatch repair, N-glycan biosynthesis, spliceosome and nucleotide excision repair were the significantly enriched pathways. In the PPI network, CTSS, CD53, IGSF6, PTPRC and LAPTM5 were the hub nodes. Intracellular protein transport and RNA splicing via transesterification reactions were closely associated with IPD. The DEGs, such as CX3CR1, SLC5A7, CD53 and PTPRC may be the potential targets for IPD diagnosis and treatment.