Retinoic acid (RA) is a teratogen which can induce cleft palate. Recent studies suggested that gamma amino butyric acid (GABA) was involved in the development of palate. If the GABA signal pathway participates the cleft palate induced by RA remains to be elucidated. In the present study, we investigated the effect of all-trans retinoic acid (atRA) (0.2, 0.67, 2.0 and 6.7 μmol/L) on cell proliferation and apoptosis, and then examined the role of gamma amino butyric acid (GABA) signaling pathway in regulation of cell proliferation and apoptosis by atRA in murine embryonic palate mesenchymal (MEPM) cells. Results showed that atRA (2 μmol/L and 6.7 μmol/L) significantly inhibited cell proliferation and increased apoptosis. The mRNA and protein expression of glutamic acid decarboxylase 67 (GAD 67) which was a key enzyme in synthesis of GABA were significantly down regulated by atRA (0.67, 2.0 μmol/L and 6.7 μmol/L). But the mRNA and protein expression of GABAAR-β3 were shown no obvious change compared with the control group. When GABA (1.0 μmol/L) was added to cell culture system, the effect of atRA (6.7 μmol/L) on the proliferation and apoptosis of MEPM cells was reversed. In conclusion, all-trans retinoic acid inhibits cell proliferation and promotes cell apoptosis through gamma amino butyric acid pathway in murine embryonic palate mesenchymal cells.