Rationale Activation of 4-1BB (CD137), one of tumor necrosis factor receptor superfamily members expressed on activated T cells, has been suggested to suppress antigen-specific helper T cells and T cell dependent humoral immune response. We investigated the anti-inflammatory effect of agonistic anti-4-1BB antibody in a murine asthma model. Methods Balb/c mice were immunized intraperitoneally with ovalbumin (OVA) at day 1 and 14 and challenged with inhaled OVA at day 27, 28, and 29 (group I). The agonistic anti-4-1BB antibody was administered immediately after OVA immunization at day 1 (group II). OVA-specific serum IgE and IgG1 levels were measured at day 30. The value of enhanced pause on methacholine challenge, differential cell counts of bronchoalveolar lavage (BAL) cells, and histopathological scores of the lungs were also assessed. The cytokine production was analyzed in the lymphocytes obtained from perihilar lymph nodes. Results In group II, OVA-specific serum IgE and IgG1 were nearly abolished. However, no significant differences were observed between the groups in the differential cell counts and IL-4 and IL-5 concentration of BAL fluids, in the histopathological scores of the lungs, and in airway hyperresponsiveness. The total number of lymphocytes and IL-5 production were decreased in group II when the regional lymphocytes were cultured with OVA. Conclusions Intervention of 4-1BB pathway might offer a novel therapeutic approach to control allergic inflammation.