T helper type 2 (Th2)-polarizing glycolipid OCH reduces disease severity in intra-abdominal sepsis (IAS). C57BL/6 (B6) mice were injected concomitantly intraperitoneally with faecal slurry (FS; 500 μl of 90 mg/ml solution) to induce intra-abdominal sepsis (IAS), and vehicle, OCH or KRN7000. (a) OCH-treated mice had prolonged survival significantly compared to vehicle- and KRN7000-treated mice (n = 19, n = 15, n = 8 for OCH, vehicle and KRN7000 groups, respectively). ***P < 0·001 by log-rank test. (b) OCH-treated mice demonstrated significantly reduced disease severity compared to vehicle-treated and KRN7000-treated mice (n = 19, n = 15 and n = 8 mice, respectively, for OCH, KRN7000, and vehicle groups). ***P < 0·001 by two-way analysis of variance (ANOVA) with Bonferroni post-test. (c) iNK T-deficient Jα18–/– mice were given FS (500 μl of a 90 mg/ml solution) to induce IAS and treated concomitantly with OCH or vehicle. Murine sepsis scores were similar between vehicle and OCH-treated mice (n = 3 per group). (d,e) Administration of OCH and KRN7000 resulted in significantly reduced detection of CD3+CD1d tetramer+ invariant natural killer T (iNK T) cells among septic B6 mice compared to vehicle treatments. The percentages of CD3+ T cells remained unchanged with administration of iNK T-specific glycolipid agonists (n = 6, n = 4, n = 6, and n = 3 for vehicle, OCH, vehicle (KRN7000) and KRN7000 groups, respectively). *P < 0·05; **P < 0·01 by Mann–Whitney U-test. (f) Bacterial counts in blood and multiple organs were similar between vehicle-, OCH- and KRN7000-treated mice with sepsis (n = 7–9 per group). Data are representative of at least three independent experiments.