To improve efficacy, especially for the cell-mediated response to inactivated viral vaccines, a modified levamisole (LMS) adjuvant formulation, designated LMS+, was evaluated for its efficacy in mice and chickens, using Newcastle Disease Virus (NDV) as a model pathogen. Compared with oil adjuvant, the killed NDV in LMS+ induced a significantly higher helper T cell type 1 response, as shown by higher levels of interleukin-2, interferon-gamma, T cell proliferation, and delayed-type hypersensitivity responses, without sacrificing the level of IgG production in mice. In addition, vaccine in LMS+ formulation increased the expression of MHC and costimulatory molecules as well as the number of CD11c+ dendritic cells, suggesting that the better response to the LMS+ formulation occurs partly via the maturation of dendritic cells and activation of MHC-antigen presentation and costimulation. Furthermore, this formulation provides 100% protection in chickens after challenge with a lethal dose of virulent NDV strain F48E9 at 1000 ELD50 (50% egg lethal dose). These results demonstrated that modified LMS+ adjuvant could be used to improve both humoral and cell-mediated responses for inactivated viral vaccines and its development as an effective inactivated viral vaccine is warranted.