Background Idiopathic hyperoxaluria (IH) may be caused by increased endogenous formation or exogenous absorption of oxalic acid. Characterization of the molecular pathogenesis of IH has been hampered by the lack of an ideal animal model. We therefore established a stabile rat IH model in order to analyze variation in gene expression profile in the jejunum and to investigate the association between IH pathogenesis and exogenous absorption of oxalic acid. Methods A rat model of IH was established and three female rats with IH were assigned to the study group, while three normal rats served as controls. Total RNA was isolated from the jejunum of rats in the two groups and mRNA was purified, reversely transcribed, labeled with Cy5 or Cy3 and hybridized to 27K Rat Genome Array. Differences in gene expression profile between the 2 groups were analyzed by bioinformatics methods. Results Comparative analysis revealed that the expression of 517 genes was up-regulated and that of 203 genes was down-regulated by at least two-fold in the jejunum of rats with idiopathic hyperoxaluria. These genes are related to many functions including cell signal transduction, DNA binding and transcription, ATP binding, ion binding and transport, cell receptors, immunity, cyclins, cytoskeleton structure, and metabolic proteins. Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis revealed that the variations of 239 pathway functional changes are statistically significant (P <0.05). Conclusions cDNA microarray can be used effectively to screen differentially expressed genes in the jejunum of rats with idiopathic hyperoxaluria. These differentially expressed genes may underlie idiopathic hyperoxaluria pathophysiology and provide a platform for further studying molecular pathogenetic mechanisms. Chin Med J 2012;125(2):312-315