Unlike polyphenols which are widely available in the diet, polyacetylenes are available only from the Apiaceae family vegetables, including carrot, parsnip, fennel, celery and many herbs (parsley, lovage etc). The aim of this study was to investigate the hypothesis that polyacetylene falcarinol reduces intestinal inflammation and examine its similarity of effect to isothiocyanate R-sulforaphane, during the late phase of acute inflammation. To this end, three month old male CB57BL/6 mice were fed twice daily for one week with 5 mg/kg of either FA, SF or vehicle before receiving an intraperitoneal injection of 5 mg/kg endotoxin (lipopolysaccharide) to induce modest acute inflammation. The expression of intestinal and hepatic heme oxygenase-1 at the mRNA and protein levels, circulating cytokines, as well as intestinal and mesenteric n-6 and n-3 fatty acid lipid mediators were compared 24 hours after LPS administration to examine their effects on the late phase of inflammation. Intestinal Nrf2 target enzyme heme oxygenase-1 was upregulated 8.42-fold at the mRNA level and 10.7-fold at the protein level by falcarinol supplemented diet. However, the falcarinol-supplemented diet produced a unique type-2 plasma cytokine skew after LPS treatment. Plasma cytokines IL-4, IL-13, IL-9 and IL-10 were upregulated, reflecting the cytokine profile of reduced type-1 inflammation. A detailed lipidomic analysis of n-6 and n-3 fatty acid pro- and anti-inflammatory pathways in the mesentery and intestinal mucosa showed that falcarinol diet was more similar to the control groups than to other LPS treated groups. In this study we demonstrated that falcarinol-supplemented diet produced a unique immunomodulatory effect not observed with sulforaphane in late phases of inflammation. These results support the hypothesis that falcarinol may have role as a dietary immunosuppressant in patients with inflammatory gastrointestinal as well as other inflammatory disorders that may be alleviated by increasing carrot consumption or other falcarinol-containing food sources.