Objective: To observe the morphologic changes of pituitary adrenocorticotrophic hormone (ACTH) cells in Wistar rats at different altitudes, and clarify the mechanism of stress reaction to hypoxia in ACTH cells. Methods: Wistar rats were divided into three groups and moved to different altitudes (1700 m, 3100 m, 4050 m). After 12 days, changes of ACTH cells were observed by using immunohistochemisty, image analysis and electron microscopy. Results:The ratio (R) of immunoreactive cell area to scanned area and mean optical density (A) increased at higher altitude with statistically different R values between groups of 1700 m and 4050 m (P