Adjuvant play an important role in the efficacy of vaccines, the protective immune response produced by vaccines can vary according to the kinds of adjuvant. The comprehensive sero-immunological study was conducted to reveal the adjutant’s effect of Clinoptilolite and oil on the immune response of trivalent Foot and mouth disease (FMD) vaccine in cattle. This study was conducted in five cattle groups; The first group was vaccinated intramuscularly (I/M) with trivalent FMD Clinoptilolite (1 μg/dose) vaccine, The second group was vaccinated with FMD (Oil + Clinoptilolite) vaccine and Third group was vaccinated with FMD oil vaccine while the fourth group were non vaccinated used as negative control and fifth group were used for safety test. Then conducted tests to compare the enhancement in cattle immunity. The humeral and cellular immune responses were monitored in different tested groups. The obtained results indicated that the incorporation of Clinoptilolite into inactivated FMD vaccine induces an increase of the specific protective immune response. Higher and longer period of immune responses were found in cattle vaccinated with both Montanide oil and Clinoptilolite adjuvanted vaccine up to 40 weeks, while those vaccinated with Clinoptilolite or oil vaccine showed protected immunity up to 32 weeks respectively. Finally, we recommended that using of Clinoptilolite with oil as a potential adjuvant in FMD vaccine.