This study aims to investigate the mechanism of hypothalamic Leptin/Ghrelin and arcuate nucleus pro-opiomelanocortin (POMC) system in the regulation of high-altitude acclimatization. SD rats (male) were divided into two groups and separately fed at the 2260m and 4700m altitude. Tow groups contained 5 small groups separately, including 1 d, 3 d, 7 d, 15 d and 30 d, and 8 rats in each group. Blood, cerebrospinal fluid and tissues were taken at setting time. Leptin and Ghrelin were detected by using radioactivity immuno-assay. RNA expression of NPY and POMC were detected by using RT-PCR assay. The number of NPY positive neurons was detected by using immunofluorescence (IF) and cell counting. Other rats were sent to the 4300m and fed in animal room with regular diet and drinking. The results indicated that after being sent to high altitude region, Leptin levels at the 3rd and 7th day were significantly higher than the 1st day, while decreased at 15th, and the level at 30th day was closed to the 1st day. Ghrelin levels decreased at the 3rd, 7th and 15th day, and were lower at the 30th day. Comparing to the 1st day, NPY transcription levels increased at the 7th day, while decreased at the 30th. POMC transcription level decreased at the 7th day, while increased at the 30th gradually. The feeding of the rats fed at the 4300m decreased at the 3rd and the 5th, while increased at the 7th, 15th and 30th day. The weight of the rats changed as the feeding changing. In conclusion, after being sent to the high region, the rats were adaptive to the hypoxia environment gradually, and the steady of neuro-endocrine regulation recovered or established.