Direct inhibitory effects of tannic acid on Haemonchus contortus viability were studied in vitro using the larval migration inhibition (LMI) assay. Sheep white blood cells (WBC) were preincubated with 5 and 50 lg/mL tannic acid or not followed by whole H. contortus antigen (WHA). Cells were harvested at 24 h post-incubation to test host immune responses. Concentrations of 50, 100, 500, 1000, 3000 and 5000 lg/mL tannic acid inhibited larvae migration by 19.8, 42.4, 46.3, 92.0, 93.7 and 100%, respectively, within 96 h post-incubation (P < 0.001). The relative mRNA levels of interferon (IFN)-c, interleukin (IL)-2, IL-4 and IL-10 were increased by WHA stimulation without tannic acid. However, the increased effects on IFN-c and IL-2 were inhibited by tannic acid preincubation (P < 0.001), while the increases in IL-4 and IL-10 were greatly enhanced by tannic acid preincubation (P < 0.001). Changes in protein levels of all cytokines essentially paralleled the changes in their corresponding mRNA levels. In conclusion, tannic acid is directly harmful to larvae in a dose- and time-dependent manner and modulates immune responses of sheep WBC stimulated by H. contortus antigen by inhibiting Th1 cytokines and increasing Th2 cytokine expression in vitro.