Vitamin E modulates the immune response, in part by reducing inflammation. The bacterial component lipopolysaccharide (LPS) can induce an inflammatory response in chickens. The objective of this study was to evaluate immunomodulatory effects of dietary type and level of vitamin E on response of broilers to LPS. One-day-old broiler males (n = 96) were placed in a vitamin E-type (synthetic, natural) × vitamin E level (22, 220 IU/kg) × LPS (LPS, saline) block design. At 22 d, LPS (or saline) was injected subcutaneously. Spleens were harvested for RNA isolation at 3 and 24 h postinjection. Relative levels of RNA expression were measured for the immune-related genes: avian β defensin 10 (AvBD10), interleukin 6 (IL6), interferon-γ (IFN-γ), inducible nitric oxide synthase (iNOS), interleukin 10 and transforming growth factor- β1 (TGF-β1). Avian β defensin 10 and iNOS are innate antimicrobial proteins. Interleukin 6 and IFN-γ are pro-inflammatory cytokines, whereas interleukin 10 and transforming growth factor-β1 are anti-inflammatory cytokines. There were significantly higher splenic levels ofIL6,IFN-γ,iNOS, andIL10 RNA expression at 3 h postinjection in chickens receiving LPS than in chickens 24 h post-LPS injection or saline-injected birds at either time. These data suggest that LPS induced an immune response that was regulated by both pro- and anti-inflammatory cytokines. Birds fed natural-type (versus synthetic) vitamin E had a significantly lower LPS-induced inflammatory response, as indicated by lowerIL6 RNA expression levels, suggesting a protective effect from natural-type vitamin E when a chicken encounters a bacterial component.