This study aimed to detect the expression and distribution of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR-2), and erythropoietin (EPO) proteins in small intestinal tissues of 50-day-old, newborn, and adult yaks. The results provide basic data for the study of the relationship between adaptability and age of plateau yak. Small intestine tissues from healthy adult, 50-day-old, and newborn yak were collected and embedded in paraffin sections. Histological features were observed by haematoxylin and eosin staining. The expression of VEGF, VEGFR-2, and EPO proteins were detected by immunohistochemical staining. Immunohistochemical results showed that of the expression VEGF, VEGFR-2, and EPO were detected in the small intestinal villi of yaks at all ages. The EPO expression level in the jejunum and duodenal villous epithelial cells of newborn yaks was significantly higher than that of 50-day-old and adult yaks. The EPO expression level in ileum villous epithelial cells of 50-day-old yaks was significantly higher than that of newborn and adult yaks. VEGF expression in newborn yak ileum and jejunum epithelial cells of the intestinal villus were significantly higher than in the 50-day-old and adult. In the 50-day-old yaks, the duodenal intestinal villus epithelial cells expression levels were higher than in the adult and newborn yaks. The expression level of VEGFR-2 in the ileum, jejunum and duodenal villous epithelial cells of 50-day-old yak was significantly higher than in that of adult and newborn yak. The expression and distribution characteristics of EPO, VEGF, and VEGFR-2 in yak intestinal tissues of different ages indicate that these proteins may be involved in the physiological regulation of yak intestines in hypoxic environments. It may be an important regulatory protein in yak adaptation to a high altitude and low oxygen environment.