Objective: To investigate the value of serum aquaporin-4 (AQP4) antibody, myelin oligodendrocyte glycoprotein (MOG) antibody, myelin basic protein (MBP) antibody and glial fibrillary acidic protein (GFAP) antibody in differential diagnosis of central nervous system demyelinating diseases. Methods: A total of 1368 patients with demyelinating diseases of the central nervous system were selected as the research objects. Four kinds of antibodies in serum samples were detected by indirect immunofluorescence method with cell transfection, and the detection results were analyzed. Results: The total pos. rate of antibodies was 24.93% in 1368 patients with demyelinating diseases of central nervous system. The male to female pos. rate ratio was 1.00:1.66. The average age of onset was (41.10±20.61) years old. There were five pos. combination patterns of the four antibodies in the pos. patients, which were GFAP antibody pos., MOG antibody pos., AQP4 antibody pos., GFAP+MOG antibody pos. and GFAP+AQP4 antibody pos., but no MBP antibody pos. The pos. rate of GFAP antibody in male was significantly higher than that in female (P=0.04), and the pos. rate of AQP4 antibody in female was significantly higher than that in male (P<0.05). The average onset age of patients with different antibody positivity was (27.49±19.53) years old, (39.66±19.93) years old, (48.38±15.23) years old, resp. The total pos. rate of four antibodies was the highest (46.77%), followed by myelitis (32.90%) and encephalitis (23.35%). Conclusion: AQP4 antibody, MOG antibody and GFAP antibody have important significance in the differential diagnosis of demyelinating diseases of central nervous system, while MBP antibody has little significance in the differential diagnosis of demyelinating diseases.