Toll-like receptors (TLRs) are important pattern-recognition receptors (PRRs) that could trigger innate immune response and mediate acquired immunity. TLRs signaling transduction depends on five adaptor proteins containing the TIR domain, and SARM (sterile-α and TIR motif containing protein) is the most conversed from invertebrate to vertebrate of them. The characterization of porcine SARM1 gene and its transcriptional regulation in infectious disease was less reported. In this research, the full-length CDS of porcine SARM1 gene was cloned, which encoded a polypeptide of 724aa. Porcine SARM1 gene spans 18kb containing 9 exons and 8 introns, and SARM protein localized in mitochondria. N-terminal heat armadillo repeat motif (ARM) controls the protein associated with mitochondria. RT-PCR results showed that SARM1 gene was highly expressed in brain, spleen, kidney and lung. Using the radiation hybrid (IMpRH) panel, porcine SARM1 gene was assigned to SSC12 q13, where several QTL associated with pathological damage, physiological change and meat quality were mapped. The microarray data and quantitative RT- PCR analysis revealed that the expression of SARM1 gene in pulmonary alveolar macrophages (PAM) of Tongcheng piglets decreased during artificial infection with High Pathogenic Porcine Reproductive and Respiratory Syndrome virus (HP-PRRSV). Gene-interaction network analysis of porcine SARM1 in PAM showed that the down-regulation of SARM1 gene in infected Tongcheng piglets may modulate the PAMs activation and regulate resistance genes and inflammatory genes expression. The findings show that porcine SARM1 may play an important role in PRRSV infection, so the further work should be necessary.