To observe the effect of NR2B-siRNA mediated by hydroxyapatite nanoparticles (HA) on formalin-induced inflammatory pain of mice and the expression of NR2B in spinal cord. To preliminarily investigate the feasibility of HA as siRNA carrier to transfer NR2B-siRNA in vivo. The sequence-specific NR2B-siRNA of mice was designed and synthesized initially. Using HA as a siRNA carrier, green fluorescent protein(GFP)-siRNA as the control, 4 ug of NR2B-siRNA was administered into subarachnoid space of mice via conscious injection. On 7th day after intrathecal injection, formalin test was observed for 1 hour in each group, followed by dissection of lumbar segments of spinal cords immediately for use in immunohistochemical staining of NR2B. The results show that NR2B-siRNA not only significantly abolish the nociceptive response of mice in the tonic phase induced by formalin, but also decrease the amount of cells expressing NR2B protein in spinal cord, while GFP-siRNA mediated by HA don’t produce the same effects, which demonstrates that HA is capable of effectively transfering NR2B-siRNA via intrathecal injection, furthermore, HA/NR2B-siRNA complex can significantly reduce formalin-induced pain of mice, and specificly inhibit NR2B expression in spinal cord of mice.