The aim of this exploratory work was to use a microarray-based approach to study the global transcriptome profile of caesarean-derived, colostrum-deprived (CDCD) piglets experimentally infected with porcine circovirus type 2 (PCV2). PCV2-inoculated piglets developed a subclinical infection, as confirmed by serology, in situ hybridization and quantitative PCR. Total RNA from mesenteric lymph nodes and lungs was obtained by duplicate from 2 control and 2 PCV2-inoculated piglets and was hybridized to Affymetrix Porcine GeneChip. Among the 24,123 probesets studied, 25 and 33 were found to be significantly differentially expressed (DE) between control and PCV2 groups for mesenteric lymph node and lung, respectively. Most up-regulated genes in PCV2 group were closely related to the immune response, such as cytokines (CCL4L, CXCL9, CXCL11), MHC binding molecules (TCRalpha, CD8alpha), immunoglubulins (IgG) and T cell activation (LCK, KLRK1, RASSF2, GBP2). Quantitative real-time PCR was performed to verify the microarray results. Therefore, from a transcriptional point of view, PCV2-inoculated pigs were apparently able to activate a cell-mediated response and develop PCV2-specific antibodies, which probably led to a subclinical infection. The results from this study indicate that a microarray based approach is a helpful tool in order to better understand the pathogenesis of PCV2 infection.