ABSTRACT: With the rapid development of economy, the demand for beef, with regard to quantity and quality, by consumers has been increasing in China. Chinese native cattle are characterized by their abundant genetic resources, unique origins, large breeding stocks, and robust environmental adaptability. Thus, to explore the genetic mechanisms on regulating meat quality in Chinese native cattle is of great importance to satisfy increased requirements for beef production. In this study, we investigated three breeds of cattle, namely Yunling, Wenshan, and Simmental, at the age of 12 months. Animals were classified into three groups (n = 5/breed). Growth traits including body weight and body size and plasma hormone levels were measured. Body weight of Wenshan cattle was significantly lower than that of Yunling and Simmental cattle (P < 0.05). Again, body size indexes, such as withers height, body slanting length, chest circumference, and hip and rump length, were significantly lower in Wenshan cattle than those in Yunling and Simmental cattle (P < 0.05). However, there were no significant differences in those indexes between Yunling and Simmental cattle (P > 0.05). Cattle were slaughtered at the age of 18 months and then meat color, pH, pressing losses, muscle tenderness, and cooking losses were measured at 0, 1, 2, 3, 5, and 7 days. Data revealed differences in meat quality among the three breeds analyzed. Based on transcriptomic sequencing and bioinformatic analysis, we observed 3,198 differentially expressed genes related to meat quality, of which 1,750 genes were upregulated. Moreover, we found two important signaling pathways closely linked to meat quality, namely adipocytokine signaling pathway [e.g., Leptin receptor (LEPR)] and protein processing in the endoplasmic reticulum [e.g., signal transducer and activator of transcription 3 (STAT3), heat shock protein (HSPA12A), and calpain 1 (CAPN1)]. The results of transcripts were further verified by qRT-PCR. Using correlation analysis between gene expression levels and shear force, we also identified two functional genes (e.g., HSPA12A and CAPN1) associated with meat quality. Overall, this study provides new sights into novel targets and underlying mechanisms to modulate meat quality in Chinese native cattle.