Giardia lamblia is a protozoan parasite that infects the small intestine of humans and several other mammalian hosts resulting in diarrhea, abdominal cramps and malnutrition. The parasite is very easily transmitted through contaminated water and food, resulting in a very high incidence worldwide. Most infections resolve spontaneously however, suggesting an effective immune response against Giardia lamblia infection. Interestingly, unlike most intestinal infections, Giardia lamblia does not induce significant inflammation in the gut mucosa. While adaptive immune responses have been shown to be crucial in anti-Giardia immunity, innate responses to Giardia infection have been less studied. To characterize the anti-Giardia response, we carried out Giardia-Dendritic cell (DC) co-incubation experiments and analysed DC cytokine secretion and co-stimulatory molecule expression. Compared to the potent DC activator LPS, Giardia induces only small amounts of IL-6 and TNFα, and no detectable IL-10 and IL-12. Interestingly, Giardia was found to potently inhibit the proinflammatory cytokine IL-12, while enhancing production of the anti-inflammatory cytokine IL-10 by LPS activated DCs. We show that Giardia's ability to inhibit IL-12 was partially dependent on both IL-10 augmentation and activation of phosphatidylinositol-3 kinase. To examine the role of DCs in vivo, DCs loaded with Giardia antigens were transferred to naïve hosts who were then challenged with live parasites. Adoptive transfer of DCs led to reduced infection intensity in both wild type and IL-6 deficient mice. Thus the limited activation of DCs by Giardia is sufficient to induce protective responses. Moreover, defects in IL-6 knockout mice can be traced to the development and/or function of DCs. We conclude that both DCs and IL-6 have crucial roles in anti-Giardia immunity, and that understanding the immune responses against Giardia could provide important information towards management of immune pathologies and chronic infections.