Objective To investigate the effects of co-exposure to LPS and heat on plasma tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in rats. Methods Male pathogen-free Wistar rats were randomly assigned to the following groups: saline-injected normothermic control (Group C), saline-injected heat exposure (Group H), LPS-injected normothermic control (Group L), LPS-injected heat exposure (Group HL). Mean arterial pressure (MAP) was continually monitored. Plasma levels of TNF-α, IL-6, MDA and SOD were determined at 0, 40, 80, 120 min. Results The rats in Group HL displayed much lower MAP, higher MDA and lower SOD than the other 3 groups. The rats in Group HL displayed an early rise in plasma TNF-α, IL-6 at 40 min, the peak values of both at 80 min significantly higher than the other three groups at the same time piont. Conclusion Co-exposure to LPS and heat primes the rats to advance and augment systemic inflammatory response syndrome.