Heatstroke is considered an important condition that may contribute to endothelial cell damage. The aim of this study was to assess temporal profiles of the cytokine (IL-6 and IL-8) and mRNA production when endothelial cells undergo higher temperature stimuli. In the first group, human umbilical vascular endothelial cells (HUVECs) were cultured at 4 different temperatures (37, 38, 39 or 40°C) for 1, 3 and 5 h. In the second group, HUVECs were cultured at 37°C for 4 or 23 h, after stimulation by heating for one hour at the same culture temperatures used in the first group (37 to 40°C). After culturing, IL-6 and IL-8 mRNA and protein levels were measured. It has been found the cytokine mRNA levels being significantly higher (p<0.001) in all cells incubated at higher temperatures than those in the control (cultivation at 37°C). At the same time, the production of IL-6 and 8 at a higher temperature (39, 40°C) was significantly lower (p<0.001) than at 37°C (control), and the decrease was temperature dependent. However, IL-6 and IL-8 levels were significantly greater in the cells at 23 h after transient hyperthermic (40°C, 1 h) stimulation than in control ones (p < 0.001). After a transient hyperthermia, the production of the cytokinesin HUVECs is initially inhibited and then augmented. The results indicated that tissue injury might continue to develop after a hyperthermic event. There might be a potent risk for under estimation of cytokine induced tissue injury in the acute phase of a heatstroke.