Mucosal immune system is functionally characterized by its ability to limit the access of environmental antigens such as food, airborne materials, and commensal microbes to the systemic immune compartment, leading to reduction in the magnitude of systemic immune responses. Mucosal immune system reacts at the site of antigen exposure and at anatomically distant mucosal sites by specific antibodies production and specific cellular immunity. The mucosal administration of neoantigen induces specific mucosal and systemic antibodies production and systemic effector T cells anergy accompanied by induction of regulatory T cells, phenomenon termed mucosal tolerance. Based on above observations, several studies test the ability to prevent some autoimmune diseases by mucosal administration of respective antigens but with little to no success. This review attempts to describe mechanisms involved in the induction of immune response and tolerance after immunization by mucosal routes - oral or intranasal administration. Further it aims to elucidate conditions critical for elicitation of mucosal tolerance. © Ceská lékarská spolecnost Jana Evangelisty Purkyne, Praha 2011.