Haemophilus parasuis (H.parasuis), an important swine pathogen, causes Glässer's disease leading to pulmonary fibrosis, polyserositis, meningitis, and arthritis. However, the common molecular response and reaction from the host remain unknown. In this study, to uncover novel host factors involved in H.parasuis infection, we identified the global transcriptomics of porcine lung, spleen, blood, alveolar macrophages (PAM), peripheral blood mononuclear cell (PBMC) and aortic vascular endothelial cells (PAVECs) after infection of H.parasuis (Hps0165 strains) using microarray data and high throughput sequencing from Gene Expression Omnibus (GEO), respectively. The results showed that fifteen overlapped genes were significantly regulated in H.parasuis infected porcine lung and spleen, and then were compared with the data from porcine blood, revealing RETN, TIMP1 and C4BPA play potentially an important role for H.parasuis invasion. Furthermore, through analysing porcine cells infected with H.parasuis, we uncover the only overlap gene TIMP1 remarkably upregulated in all assembled data, indicating that TIMP1 could function as key target for the treatment of H.parasuis infection.