Objective We aimed to investigate the expression levels of GABA and GABA(A) receptor alpha 1 and alpha 2 subunits in patients with major depressive disorder (MDD) during onset and remission. Materials and Methods 48 patients with MDD during onset and 45 patients with MDD during remission who were treated in our university were selected. Moreover, the control group included 46 healthy volunteers recruited in the community. The depression and anxiety symptoms were assessed by Hamilton Depression (HAMD) Scale and Hamilton Anxiety (HAMA) Scale. ELISA was used to determine the serum GABA levels. The mRNA expression of GABA(A) receptor alpha 1 and alpha 2 subunits in peripheral blood were detected by RT-PCR. Results The expression levels of serum GABA and of GABA(A) receptor alpha 1 and alpha 2 subunits in MDD depression attack group were notably decreased in comparison with those in MDD remission group and control group ((4.10 +/- 0.73) v.s. (5.91 +/- 1.25) and (5.83 +/- 1.17) umol/L, F = 5.61, p < 0.001; (0.53 +/- 0.32) v.s. (0.91 +/- 0.18) and (0.93 +/- 0.21), F = 8.37, p < 0.001; (1.45 +/- 0.86) v.s. (2.33 +/- 1.49) and (2.28 +/- 1.50), F = 8.23, p < 0.001). However, there were no marked difference in the levels of these three indices between the MDD remission group and the control group (p > 0.05). Serum GABA levels were negatively correlated with HAMA total score (r = -0.34, p = 0.02), HAMD total score (r = -0.46, p = 0.01) and depression core symptom score (r = -0.32, p = 0.03). Conclusions During the onset of MDD, there may be GABA neuronal dysfunction and abnormal expression of GABA(A) receptor subunits, and those changes showed a state change, which gradually returned to normal during remission.