Objective To investigate the effect of heat stress on organ indices, intestinal morphology, gastric mucosal HSP70 mRNA expression and glucose metabolic hormones in mice. Methods A single-factor experiment was designed for the present research. Eighteen KM mice of the similar age and weight were randomly divided into control group and heat stress group. The weight of the heart, liver, spleen, lung and kidney, as well as the expression of HSP70 mRNA in the mouse gastric mucosa were measured. The plasma concentration of insulin and glucagon, the villus height and crypt depth of the duodenum and jejunum were detected. The histological changes of the liver, duodenum and jejunum were also examined. Results There was no effect of heat stress on the organ indices. It significantly increased the expression of HSP70 mRNA in the gastric mucosa, reduced the plasma insulin level and caused serious injury to the liver, duodenum and jejunum in the mice. Conclusions Heat stress does not significantly affect the organ indices in mice, but can significantly increase the expression of HSP70 mRNA in the gastric mucosa, cause apparent damages in the liver, duodenum and jejunum, reduce the villus height, crypt depth and villus height/crypt depth ratio of the duodenum and jejunum, and also decrease the blood insulin concentration in the mice.