Abstract:CD9 and CD81 were both important candidate factors during sperm-egg fusion in mammals, but their tissue expression characteristics in vivo were still unknown. In order to elucidate their expression characteristics in sheep (Ovis aries), tissue expression of CD9 and CD81 genes in Small Tail Han sheep ewes (high fecundity) and Sunite sheep ewes (low fecundity) in the follicular phase was investigated using semi-quantitative reverse transcription polymerase chain reaction (sqRT-PCR) and quantitative real-time quantitative PCR (qRT-PCR) in the present study. The results showed that the expression of CD9 and CD81 genes was found in 14 tissues of two sheep breeds. The CD9 gene expression was the highest in oviduct tissue of two sheep breeds, and its expression in hypothalamus, pituitary and ovary tissues of Small Tail Han sheep was extremely higher than that of Sunite sheep (P<0.01). The CD9 gene expression in ovary and hypothalamus tissues was significantly higher than that in pituitary and uterus in Small Tail Han sheep (P<0.05), while its expression in hypothalamus and uterus tissues was significantly higher than that in ovary and pituitary in Sunite sheep (P<0.05). The expression of CD81 gene in reproductive axis tissues in Small Tail Han sheep was extremely higher than that in Sunite sheep (P<0.01). In Small Tail Han sheep, the CD81 gene expression was the highest in hypothalamus tissue (P<0.01), and its expression in pituitary and oviduct tissues was extremely higher than that in ovary and uterus tissues (P<0.01). While in Sunite sheep, the CD81 gene expression was the highest in ovary tissue (P<0.01), and its expression in hypothalamus was extremely higher than that in pituitary, oviduct and uterus (P<0.01). Our study preliminarily indicated that CD9 and CD81 genes maybe relate with difference of sheep prolificacy, which might provide a reference for revealing the molecular regulatory mechanism of sheep reproductive performance.