Objective To evaluate the changes in the expression of acetylated histone 3 lysine 9(H3K9Ac)and methyl-CpG-binding protein 2(MeCP2)in the spinal cord and dorsal root ganglion(DRG)of rats with diabetic neuropathic pain(DNP). Methods Pathogen-free male Sprague-Dawley rats, weighing 120-160 g, were fed a high-fat and high-sucrose diet for 8 weeks, then streptozocin 35 mg/kg was intraperitoneally injected, and type 2 diabetes mellitus was confirmed by blood glucose level≥16.7 mmol/L 3 days later.DNP model was considered successful when the decrease in pain threshold <85% of the baseline value on 14 days after injection, otherwise it was considered as non-DNP(NDNP). Eighteen rats with DNP and NDNP served as DNP and NDNP groups, respectively, and another 18 normal rats served as control group(group C). At 3, 7 and 14 days after successful establishment of the model, the mechanical paw withdrawal threshold and thermal paw withdrawal latency were measured in group DNP and at the corresponding time points in C and NDNP groups, and then rats were sacrificed, and the lumbar segment of the spinal cord and DRGs were removed for determination of the expression of H3K9Ac and MeCP2 by Western blot. Results Compared with C and NDNP groups, mechanical paw withdrawal threshold was significantly decreased, thermal paw withdrawal latency was shortened, the expression of H3K9Ac in the spinal cord and DRGs was up-regulated, and the expression of MeCP2 in the spinal cord and DRGs was down-regulated at 3, 7 and 14 days after successful establishment of the model in group DNP(P<0.05). Conclusion The maintenance mechanism of DNP may be related to up-regulated expression of H3K9Ac and down-regulated expression of MeCP2 in rats with DNP. Key words: Diabetes Mellitus; Neuralgia; Histones; Methyl-CpG-binding protein 2; Spinal cord; Ganglia, spinal