Abstract: Abstract Chicken (Gallus gallus) and duck (Anas platyrhynchos) are major hosts of Newcastal virus (NDV) disease with distinct response to infection and in which host innate immune response maybe play an important role. In order to compare the host innate immune response of chicken and duck and ensure their role of the difference in pathogenicity infected with duck-origin NDV, the message RNA expression levels of pattern recognition receptors (PRRs), cytokines, antiviral proteins and major histocompatibility complex (MHC) molecules genes in both chicken and duck peripheral bloods isolated at different times were examined by using the quantitative real-time polymerase chain reaction method. Gene expression profiles showed that duck-origin isolates (SD03) replicated more efficiently and had a significantly higher titer in chicken spleens compared with duck spleens at each time point; toll-like receptor 7 (TLR-7), interleukin 1β (IL-1β), IL-2, IL-6, IL-8, interferon β (IFN-β), MHCⅠ and MHCⅡ exhibited distinct expression patterns and different levels in chicken and duck peripheral blood; Furthermore, the expression of all examined genes, except IL-2, were greater in chicken peripheral blood. Results showed that distinct expression patterns of toll-like receptors, cytokines and antiviral proteins and the effect of difference in pathogenicity associated with innate immune response of chicken and duck to NDV infection. Meanwhile, the results are also benefit to better understand the viral pathogenesis to avian species.