Human vaccination with BioThrax requires six injections followed by annual boosters. This makes it difficult for the compliance of the immunization program and underscores the need for development of a new and optimized vaccination protocol. Current research aims to demonstrate the proof of concept to develop a needle-free mucosal immunization protocol using a murine anthrax model. A/J mice were immunized with BioThrax via an intranasal route. Sera, saliva, vaginal, and nasal washes were evaluated for protective antigen (PA) specific antibody responses by ELISA. Antigen-specific, antibody-secreting lymphocytes were measured by ELISPOT. Sera neutralization antibody titers were determined by in vitro anthrax lethal toxin (Letx) neutralization assay. Immunized animals were challenged by a lethal dose of Bacillus anthracis Sterne spores to determine the efficacy of the vaccination. Nasal mucosal immunization with BioThrax elicited robust serum and mucosal antibody responses against PA. The antigen specific antibodies neutralized anthrax Letx, as demonstrated by in vitro neutralization assays. Two doses of intranasal BioThrax were sufficient to completely protect A/J mice against challenge with 100xLD50B. anthracis Sterne spores. The data suggests that intranasal administration may be an effective immunization modality for an improved immunization program against anthrax.