Abstract: Objective To investigate the effect of ligustilide (LIG) on low potassium-induced apoptosis in primary cultured cerebellar granule neurons (CGN). Methods Apoptosis was induced by low potassium in cultured neonatal rat CGN in vitro. The CGN was divided into control/model/CGP54626+LIG and LIG group. The neuronal viability of each group was measured by MTT assay. The protein expression levels of the key insulin-like growth factor 1 (IGF)-1 signaling effectors，including the phosphorylated IGF-1 receptor (IGF-1R), Akt, ERK1/2, CREB and activated caspase 3 were examined by Western blot analysis. Results LIG ranging from 2.5 to 20 μmol/L could protect against low potassium-induced apoptosis of CGN in a concentration-dependent manner. 20 μmol/L LIG significantly induced upregulation of the phosphorylated levels of IGF-1, Akt, ERK1/2 and CREB, and downregulation of cleaved-caspase 3 expression, which could be blocked by a selective gamma-aminobutyric acid B (GABA B) receptor antagonist CGP54626. Conclusion LIG concentration-dependently protects against low potassium-induced apoptosis in CGN at least partly through GABA B receptor activation and its downstream IGF-1 signaling pathway.