OBJECTIVES: To observe the effect of heat-reinforcing needling on the expression profile of long non-coding RNA (LncRNA) in the synovial tissue of rabbits with cold-syndrome type rheumatoid arthritis (RA), so as to explore its mechanisms underlying improvement of RA. METHODS: A total of 18 New Zealand rabbits were randomly divided into normal, model and heat-reinforcing needling (acupuncture) groups, with 6 rabbits in each group. The RA model was established by injection of mixed solution (emulsifier) of ovalbumin powder(80 mg) + NaCl (20 mL) +Freund's complete adjuvant (20 mL), combined with cold compress (ice cube +crystal calcium chloride) of the knee-joint. In addition, rabbits of the normal and model groups received regular grasping and fixation in the same way as those of the acupuncture group. For rabbits of the acupuncture group, the heat-reinforcing needling stimulation was applied to bilateral "Zusanli" (ST36) for about 1 min, followed by retaining the needle for 30 min, once a day, for a total of 7 d. The rabbits' general condition was observed, and the knee joint circumference and pain threshold after intervention were measured. The knee-joint cavity effusion, synovial thickness, and internal blood flow signals were observed using a color Doppler ultrasound apparatus. Histopathological changes of synovium were observed using H.E. staining. The contents of serum tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 were detected using enzyme linked immunosorbent assay (ELISA), and the differential LncRNAs and biological functions in the synovial tissues were detected and analyzed using high-throughput sequencing technology. The expression levels of 5 significantly differentially expressed LncRNAs were verified using qPCR. RESULTS: Compared with the normal group, the model group of rabbits showed a significant increase in the knee joint circumference ( CONCLUSIONS: The heat-reinforcing needling can regulate the expression profile of LncRNAs in the RA synovial tissue, which may be one of the mechanisms underlying inhibition of synovial inflammatory response and improvement of symptoms.