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Foot-and-mouth disease (FMD) is a severely contagious viral disease that mainly affects cloven-hoofed livestock and wildlife. Foot-and-mouth disease is an endemic disease in Iran that sometimes caused considerable losses of livestock, especially in young animals. In this study mRNA expression of interleukin-2 (IL-2) and interleukin-12 (IL-12) cytokines was evaluated in vaccinated guinea pigs with inactivated type O FMD vaccine (without adjuvant). Blood samples were collected from saphenous vein of eight male guinea pigs (at control and vaccinated groups) at 7 and 28 days after the first vaccination. Total mRNAs were extracted using the column RNA isolation kit and subsequently reverse-transcribed into cDNA. Then relative real-time PCR assay was used to analyze of quantification of IL-2 and IL-12 expression. The expression of IL-2 gene had not significant difference in vaccinated animals compared to the control group in the first and second blood samples but IL-12 gene expression significantly increased (P<0.05). Evaluation of cytokines genes expression can be as a valuable adjunct for assessment of effects of new vaccines on immune system in future studies.