Yak endometritis seriously affects yaks’ reproductive performance, causing serious economic problems for the industry. By now, many studies explored the molecular mechanism of endometritis in dairy cows, but limited studies have focused on the regulation of microRNA (miRNA) in yak endometritis. For this reason, the distinguished expressing genes were uncovered by utilizing high-throughput RNA sequencing and validated through quantitative real-time PCR. The findings revealed that uterine epithelial tissue sections from yaks with endometritis had epithelial damage, epithelial bleeding, a high number of inflammatory cell infiltration, and other pathological changes compared to the healthy group. In this study, we identified 114 (p<0.05) and 73 (p<0.01) clearly different RNAs between the healthy group and the disease group, such as bta-miR-22-3p, bta-miR-96, bta-miR-223, and bta-miR-21-3p. The enrichment analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes revealed that the targeted miRNAs were enriched in different groups, such as cell surface receptor signaling pathway, calcium ion transmembrane transport, adrenergic signaling in cardiomyocytes, protein digestion and absorption, and so on. These results provide a theoretical basis for a deeper understanding of the pathogenesis of yak endometritis, exploring new ideas for specific miRNAs as an effective treatment and diagnosis of yak endometritis, and provides reference significance for the treatment of yak endometritis in the future.