The purpose was to investigate the influence of brain asymmetry on hypothalamic-pituitary-adrenal (HPA) axis and the functions of macrophage under predator stress. The paw preference test was used to select right-pawed, left-pawed, and ambidextrous-pawed mice. After acute (45 min, once), chronic (45 min, once a day, for two successive weeks) predator stress by cats, mice were sacrificed and the blood and peritoneal macrophages were collected. The levels of plasma corticosterone and nitric oxide (NO), IL-1beta in the supernatants of cultured peritoneal macrophage were respectively detected by enzyme immunoassay (EIA) nitrate reducase method and enzyme-linked immunosorbent assay ( ELISA). The results showed: (1) The level of plasma corticosterone. In the acute predator stress group, the levels of plasma corticosterone were higher in right and ambidextrous-pawed mice than that of left-pawed mice as well as corresponding normal control group (P < 0.05), and that of the right-pawed mice was the highest, but that was decreased in left-pawed mice; after chronic predator stress, in right and ambidextrous mice, the levels of corticosterone were higher than those of the corresponding normal control (P < 0.05), and the left-pawed and ambidextrous-pawed mice's were also higher than those of the corresponding acute predator stress group (P < 0.05). (2) Level of NO. In the acute predator stress group, the level of NO in the supernatants of cultured peritoneal macrophage in right pawed mice was significantly higher than that of left-pawed mice (P < 0. 05); after chronic predator stress, those in left, right, and ambidextrous mice were higher than those of the corresponding normal control group (P < 0. 05), and in right-pawed and ambidextrous-pawed mice were also higher than those of the corresponding acute predator stress group (P < 0. 05). (3) Level of IL-1beta. In the acute predator stress group, the levels of NO in the supernatants of cultured peritoneal macrophage in left-pawed mice were significantly lower than that of the corresponding normal control (P < 0.05); after chronic predator stress, that in right-pawed mice was significantly higher than that of the corresponding normal control group (P < 0. 05). In conclusion, brain asymmetry may affect the activity of HPA axis and the functions of macrophages in Balb/c mice exposed to their predator, cat, stress.