Porcine deltacoronavirus induces TLR3, IL-12, IFN-α, IFN-β and PKR mRNA expression in infected Peyer's patches in vivo. Porcine deltacoronavirus (PDCoV) is a newly identified swine enteropathogenic coronavirus that causes watery diarrhea in piglets and results in significant economic losses to the pig industry. Currently there are no effective treatments or vaccines for PDCoV. In particular, the pathogenesis of PDCoV infection is still largely unknown. In this study, we reported that inoculating conventional weaned piglets with 1 × 109 TCID50 of the PDCoV CHN-GD-2016 strain by oral feeding could cause severe diarrhea. Virus RNA was detected in rectal swabs from 1 to 7 days post inoculation. In addition, microscopic lesions in small intestine were observed, and viral antigen also detected in the small intestines with PDCoV immunohistochemical staining. Importantly, PDCoV significantly induced mRNA expression of TLR3, IL-12, IFN-α, IFN-β, and PKR, the genes involved in modulation of the host immune responses, in infected Peyer's patches at 3 d.p.i., indicating that Peyer's patches play an important role in PDCoV immune responses in vivo. Collectively, our findings suggest that the observed gene expression profile might help explain immunological and pathological changes associated with PDCoV infection.