Objective Yak (Bos grunniens) is an indigenous mountain species and genetically adapted to high altitude. When cattle from low altitude is taken to a high altitude, it may develop hypoxic pulmonary artery hypertension known as brisket disease. We compared the morphological and histological variations of carotid body (CB) among yaks, migrated cattle and low altitude cattle. The results could provide important insights of the process of adaptive evolution. Methods The CBs were sampled from 9 indigenous yaks born and lived at 3000-4000 m, and 9 cattle whose ancestors migrated to high altitude at 2500m for several generations in Qinghai-Tibet plateau. In addition, 12 CBs of low altitude cattle living at 1300 m in Gansu were used as control. The samples were fixed, sectioned, stained, observed under an optical and an electron microscope. The expression of hypoxia-inducible factor-1α (HIF-1α), nitric oxide synthase (NOS), leptin receptor (LEPR) and erythropoietin (EPO) were observed by immunohistochemical methods. Results No significant difference was observed for the size of CB in yaks which lived in various altitude. Furthermore, the size, shape, and the percentage of chief cells and sustentacular cells from each CB of yaks had no significant difference either. However, the CB size of migrated cattle was the largest comparing to the lowland cattle and yaks. The CB of yaks was the smallest at size. The percentages of light chief cells, dark cells, pyknotic cells of each CB in yak were 67.1%∶28.2%∶4.7%, and that in migrated cattle were 78.5%∶18.6%∶2.9%, while that in lowland cattle were 87.3%∶10.2%∶2.5%. Similar to CB of lowland cattle, a small amount of clear cells of yak were of clear cytoplasm; and nuclear chromatin of dark cells was denser with more particles. In the CB in migrated cattle, the clear cells were mostly of clear cytoplasm, and few particles were investigated in nuclear chromatin of dark cells, but there were no distinct difference in sustentacular (type 2) cells from CB in these three species. Compared with lowland cattle, a small amount of nucleus heterochromatin of chief cells (type 1) in CB in migrated cattle increased. Some of chief cells exhibited anomalies in morphology. Intracytoplasmic organelles of chief cells were mostly swelling and dissolved, which resulted in small remnant of organelle and dense core vesicles. The expression of HIF-1α, NOS, LEPR and EPO varied in CB in these three species, while the positive expression rate of EPO in CB from yak was below that from lowland cattle（P<0.05）. Conclusion High altitude does not cast significant influence on the size of CB and the amount of chief cells in CB of yak. There is a certain extent of convergence in the ratio of different types of chief cells in CB between yak and migrated cattle, but the functional system of the type 1 cells is damaged because of the hypoxia in migrated cattle, suggesting that migrated cattle are experiencing the process of acclimatizing themselves to high altitude. Chronic hypoxia may affect the EPO protein expression in the CB from yak and migrated cattle.