Toxoplasma gondii infection results in an infiltration of immune cells. The mechanisms responsible for triggering inflammatory cell infiltration in T. gondii infection are not fully understood. We report that T. gondii-infected HeLa cells induced nuclear factor-kappa B (NF-kappaB) activation and increased the expression of interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) mRNA. An inhibitor of NF-kappaB activation, calpain-1 inhibitor, blocked the chemokine secretion induced by live T. gondii. Activation of the IL-8 and NF-kappaB transcriptional reporters was suppressed in cells co-transfected with IkappaB kinase beta and the IkappaBalpha super-repressor plasmids. Moreover, the addition of IL-1alpha increased NF-kappaB activation and IL-8 mRNA expression in T. gondii-infected HeLa cells. These results suggest that NF-kappaB is a central regulator of the chemokine response in T. gondii-infected human epithelial cells and that chemokine IL-8 and MCP-1 secretion might be involved in the pathogenesis of T. gondii, via the recruitment of neutrophils, monocytes, and lymphocytes.