Marek's disease virus (MDV), a highly cell-associated lymphotropic α-herpesvirus, is the causative agent of Marek's disease (MD) in domestic chickens. MDV replicates in chicken cells and establishes a latent infection within CD4+ T cells. Although MD vaccines have been in use for several decades, the exact mechanism of vaccine-induced protection is unclear. It is believed that the innate immune system plays a role in vaccine-induced immunity against pathogenic strains of MDV. To shed light on the possible function of the innate immunity in vaccine-mediated protection, we investigated the effect of vaccination, Rispens/CVI988, on the activation of cellular components of the innate immune system by analyzing the expression pattern of select immune-related genes in the cecal tonsils (CT) and duodenum of two MD-susceptible and MD-resistant chicken lines at 3, 5, and 10 days postvaccination (dpv). The differential expression patterns of the tested genes within the CT and duodenum of vaccinated birds revealed the activation of the innate immune system in both the susceptible and resistant lines. Stronger innate immune response was induced within the CT of the vaccinated birds of the susceptible line at 5 dpv. Upregulation of some of the tested genes at 10 dpv was likely due to the activation and response of the adaptive immune system to vaccination. Immunohistochemical analysis showed no increase in the number of CD3+ T cells in the CT and duodenum of the vaccinated birds of either line at 5 dpv. There was, however, an increase in the macrophage populations within the duodenum of the vaccinated birds of both the susceptible and resistant lines at 5 dpv. The vaccine strain antigen was detected in the CT and duodenum of the susceptible line, but not the resistant line at 5 dpv.