Objective: To examine the effects of the combination of quercetin(Q), cinnamaldehyde(C) and hirudin(H), a Chinese medicine formula on high glucose(HG)-induced apoptosis of cultured dorsal root ganglion(DRG) neurons. Methods: DRG neurons exposed to HG(45 mmol/L) for 24 h were employed as an in vitro model of diabetic neuropathy. Cell viability, reactive oxygen species(ROS) level and apoptosis were determined. The expression of nuclear factor of Kappa B(NF-κB), inhibitory kappa Bα(IκBα), phosphorylated IκBα and Nf-E2 related factor 2(Nrf2) were examined using reverse transcription-polymerase chain reaction(RT-PCR) and Western blot assay. The expression of hemeoxygenase-1(HO-1), interleukin-6(IL-6), tumor necrosis factor(TNF-α) and caspase-3 were also examined by RT-PCR and Western blot assay. Results: HG treatment markedly increased DRG neuron apoptosis via increasing intracellular ROS level and activating the NF-κB signaling pathway(P<0.05). Co-treatment with Q, C, H and their combination decreased HG-induced caspase-3 activation and apoptosis(P<0.05 or P<0.01). The expressions of NF-κB, IL-6 and TNF-α were downregulated, and Nrf2/HO-1 expression was up-regulated(P<0.05 or P<0.01). QCH has better effect in scavenging ROS, activating Nrf-2/HO-1, and down-regulating the NF-κB pathway than other treatment group. Conclusions: DRG neurons’ apoptosis was increased in diabetic conditions, which was reduced by QCH formula treatment. The possible reason could be activating Nrf-2/HO-1 pathway, scavenging ROS, and inhibition of NF-κB activation. The effect of QCH combination was better than each monomer or the combination of the two monomers. Objective: To examine the effects of the combination of quercetin (Q), cinnamaldehyde (C) and hirudin (H), a Chinese medicine formula on high glucose (HG) -induced apoptosis of cultured dorsal root ganglion (DRG) neurons. DRG neurons exposed to HG (45 mmol / L) for 24 h were employed as an in vitro model of diabetic neuropathy. Cell viability, reactive oxygen species (ROS) level and apoptosis were determined. The expression of nuclear factor of Kappa B -κB), inhibitory kappa Bα (IκBα), phosphorylated IκBα and Nf-E2 related factor 2 (Nrf2) were examined using reverse transcription- polymerase chain reaction (RT-PCR) and Western blot assay. The expression of hemeoxygenase- 1), interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and caspase-3 were also examined by RT-PCR and Western blot assay. Results: HG treatment markedly increased DRG neuron apoptosis via increasing intracellular ROS level and activating the NF-κB signaling pathway (P <0.05). Co-treatment with Q, C, H and their c The expressions of NF-κB, IL-6 and TNF-α were downregulated, and Nrf2 / HO-1 expression was up-regulated (P <0.05 or P <0.01) P <0.05 or P <0.01). QCH has better effect in scavenging ROS, activating Nrf-2 / HO-1, and down-regulating the NF-κB pathway than other treatment groups. Conclusions: DRG neurons’ apoptosis was increased in diabetic The possible of could could be activating Nrf-2 / HO-1 pathway, scavenging ROS, and inhibition of NF-κB activation. The effect of QCH combination was better than each monomer or the combination of the two monomers.