Abstract: Gamma-aminobutyric acid (GABA) can change the iron concentrations in the rat brain, but little is known about the mechanism. Based on our previous data, divalent metal transporter 1 (DMT1) might be associated with the changes of brain iron metabolism induced by GABA, but its regulation mechanism remains unknown. To investigate the effect of GABA on iron metabolism and its regulation mechanism in PC12 cells, the cell viability, total iron contents, non-transferrin-bound iron (NTBI) uptake and the expression of iron metabolism related proteins were examined by using MTT assay, ICP-MS, radioactive 55Fe liquid scintillation counting analysis and Western blot methods. Data showed that GABA induced increases in total iron content and NTBI uptake, as well as an increase in DMT1 expression in PC12 cells. Further investigations revealed that NF-B was translocated into the nucleus of PC12 cells treated with GABA. These findings suggest that DMT1 may be the key molecule in the regulation of iron metabolism in PC12 cells treated with GABA and that the increase of DMT1 expression is the cause of the increased NTBI uptake. Moreover, NF-kB was involved in the regulation of DMT1 in PC12 cells after GABA treatment.