Tetradenia riparia is a plant that is used as a traditional medicine in South Africa to treat inflammatory and infectious diseases. The extracts and essential oil of this plant have shown antioxidant, anticarcinogenic, and antimicrobial properties. Some infections that resolve depend on the specific pathogens and host immune response balance, but only a few studies have screened the immunomodulatory effects of T.riparia. Thus, we studied the immunomodulatory effects of T. riparia essential oil (TrEO) on macrophages. Murine peritoneal macrophages were incubated with 30 ng/ml TrEO for 3, 6, and 24 h. Cytokine expression and production were determined by semiquantitative reverse-transcriptase polymerase chain reaction and flow cytometry, respectively. TrEO affected cytokine synthesis at all time points, whereas mRNA expression was altered only at 3 and 6 h. Interleukin (IL)-1β, IL-12, IL-17, and interferon-γ expression were highly induced by TrEO at 3 h. Only IL-1β expression was elevated at 6 h, and its production gradually increased until 24 h. IL-2 was produced at high levels in the initial response, and granulocyte monocyte colony stimulating factor and IL-17 were produced at high levels at 24 h. TrEO inhibited IL-10. These results indicate that TrEO can modulate proinflammatory cytokines and downregulate IL-10 and IL-6. This profile is associated with stimulation of the innate cellular immune response and T H 2 cell suppression. The essential oil from T. riparia may be an alternative therapy for carcinogenic, autoimmune, and infectious diseases in which cellular responses are critical for their resolution.