As one of the most severe infectious diseases in the poultry industry, Newcastle disease (ND) causesa significant economic loss worldwideeven with the extensive implementation of vaccine. Tofind targets to improvegenetic resistance to NDto enhanceprotection in chickens, gene expression was analyzedin spleen of two chickenlines which differed in their resistanceto ND. The comparison of gene expression between two treatments(challenged or non-challenged)inthe two chicken lines at 2 and 6 days post-inoculation (dpi) suggeststhat thatt he mostdramatic changes ofgene expression occurredin Leghorn chickens at 2dpi.Theidentifieddifferentially expressed genesthat regulatesplenicresponse toNDVprovidepotential avenuestobreedNDV-resistantchickens in the future.