The effects of heat stress on the neurons in hippocampal CA1 region of brain ischemia/reperfusion were explored. The mice were pretreated with heat stress followed by ischemia/reperfusion by clipping bilateral cervical commo n arteries for 7 min. Mice were divided randomly into four groups as follows: (1) normal control group; (2) heat stress pretreated subsequent to ischemia/reperfusion group (HS/IR); (3) ischemia/reperfusion group (IR); and (4) heat stress group (HS). Animals in the last three groups were subdivided into three subgroups: 1 d, 4 d, 14 d respectively. The Morris water maze was used to test the ability of learning and memorizing, Nissl staining was used to count the average number of survived neurons in hippocampal CA1 region, and immunohistochemistry combined with image analysis system to detect the changes of Microtubule associated protein 2 (MAP-2) expression. The results showed that mice in IR group exhibited increased escape latency when compared with that of normal, HS and HS/IR groups (<0.01), and the mice in IR group adopted an inefficient search strategy, major in circling and restricted searching manners. Nissl staining results showed a significant reduction in the number of pyramidal neurons in hippocampal CA1 regions in HS/IR and IR groups, with a decrease in IR group (<0.01). Compared with normal group, the expression of MAP-2 in hippocampal CA1 region obviously decreased in IR group (<0.05). The present results indicate that heat stress pretreatment can improve the spatial learning and memorizing function through protection to hippocampal neurons.