Aim: To investigate the relationship between spinal cord norepinephrine, α1 and α2 adrenergic receptors and antinociception of propofol in mice. Methods: Kunming mice were used. Antinociceptive tests were investigated with the tailimmersion test and the acetic acid-induced writhing test. The effects of subcutaneous (sc), intrathecal (ith) and intracerebroventricular (icv) injection propofol on pain threshold were observed. The influences of pretreatment with ith 6 hydroxydopamine, α1R antagonist prazosin, or α2R antagonist yohimbine on the antinociception of propofol were studied. Results: Significant antinociception was produced by propofol (25, 50 mg/kg, sc) and propofol (20, 40 μg, ith) in tail immersion test and acetic the acid-induced writhing test (P＜0.05 or P＜0.01). Icy propofol (10, 20, and 40 μg) did not produce any effect on pain threshold in mice (P＞0.05). The 6-hydroxydopamine (5 and 10 μg), prazosin (5 and 10 μg), or yohimbine (5 and 10 μg) ith alone did not affect basal tai-flick latency (TFL) in conscious mice, but significantly reduced the TFL as measured by tail-immersion test in propofol (50 mg/kg, sc)-treated mice, compared with basal TFL and ve hicle groups (P＜0.05 or P＜0.01). Conclusion: The spinal cord is a target of propofol antinociception. In mice propofol antinociception is partly mediated by spinal norepinephrine, α1R and α2R.