Insulin-like growth factor-1 (IGF-1) is a neurotrophic factor and a potent anti-apoptotic factor. IGF-1 plays an important role in promoting axonal growth from dorsal root ganglion (DRG) neurons and prevents apoptosis in DRG neurons. Whether IGF-1 could modulate Ca2+ homeostasis and apoptosis of sensory DRG neurons with excitotoxicity induced by glutamate (Glu) is still unknown. In the present study, primary cultured DRG neurons were used to determine the effects of IGF-1 on Ca2+ homeostasis and apoptosis of sensory DRG neurons with excitotoxicity induced by Glu. Intracellular Ca2+ concentration ([Ca2+]i) in isolated DRG neurons using the fluorescent Ca2+ indicator fura-3 was measured by confocal laser scanning microscope (CLSM). Procaspase-3 expression was detected by Western blot analysis. Application of 0.2 mmol/L Glu evoked an increase in [Ca2+]i, confirming the excitatory effect of Glu at this stage. The decrease of procaspase-3 expression levels after application of 0.2 mmol/L Glu suggested the apoptotic effects of Glu. These effects could be inhibited by the presence of IGF-1. In conclusion, we demonstrated that IGF-1 could modulate Ca2+ homeostasis and apoptosis of sensory DRG neurons with excitotoxicity induced by Glu. Both Ca2+ homeostasis and caspase-3 processing were implicated as the underlying neuroprotective mechanisms of IGF-1.