The immunopathology of paratuberculosis involving both humoral and cellular elements is mediated through several cytokines at the sites of lesions. The systemic immune response may not reflect the events taking place at the gut levels. The objectives of this study was to evaluate the expression of mRNA for cytokines IFN-γ, TNF-α, IL-2, IL-4, IL-6 in tissues of small intestine, mesenteric lymph nodes (MLN) and blood in 8 sheep experimentally infected with a caprine strain of Mycobacterium avium subspecies paratuberculosis and 3 uninfected control sheep. Histologically, 4 sheep had mild lesions and 2 each had moderate and severe lesions. Expression of cytokines were detected by RT-PCR using specific primers and expressed in relative units against GAPDH gene serving as control.Cytokines were expressed both in the tissues and blood of all infected and control sheep. In the intestinal tissues, mRNA for these cytokines was non-significantly increased as compared with the control sheep. In MLN of infected sheep these cytokines were better expressed 1.5 to 3 times with significantly increased levels of IL-4 as compared with the control sheep. On comparison of cytokine profiles in the small intestinal and mesenteric lymph node tissues and blood, TNF- α and IL-2 were significantly increased in the MLN, IL-4 in the blood and IL-6 in the small intestinal tissues. Increased levels of IL-4 in the blood might have inhibitory effect on the expression of IL-2. In general it was observed that levels of cytokines in the blood were more related with the profile in the MLN than those in the small intestine. Increase in the levels of Th1 and Th2 cytokine types suggests that both the cell mediated and humoral immune responses are triggered simultaneously with lot of individual variation