Objective To observe the effect of baicalin preconditioning on the neuron apoptosis and the expression of NF-κB P65 protein and its mRNA, and to explore the regulatory mechanism of the neuron apoptosis. Methods Wistar rats were randomly divided into four groups:control group,experimental autoimmune encephalomyelitis (EAE) group,dexamethasone (DXM) preconditioning group and Baicalin (BAC) preconditioning group. From the day of model establishment, every group was given preconditioning once daily for 1 week. The morbidity and neurological score were observed on the daily basis. The spinal cord was removed on day 7,14,21. RNA was extracted and the expression of NF-κB P65 mRNA was detected by RTPCR. NF-κB P65 protein was detected by immunohistochemistry and the neuron apoptosis was detected by TUNEL method. Results (1) There was no encephalomyelitis case in control group. The morbidity of EAE,DXM,and BAC group was 87. 50% ,56. 25% and 50. 00% respectively. The morbidity of DXM and BAC group was significantly lower as compared with those of EAE group ( P ＜ 0. 01). The neurological scores were 1. 56 ±0. 34 and 1. 46 ±0. 20 respectively in DXM and BAC group. The score of DXM and BAC group was significantly lower than that of EAE group (P＜0. 01). (2) Apoptotic index (Al) in EAE group on day 7,14,21 were 23. 25 ± 1. 82,63. 00 ± 4. 66 and 31. 50 ± 3. 63 respectively, which was significantly higher than the control, DXM and BAC group (P ＜ 0. 01). (3) The NF-κB P65 positive cells were less in control group,but the positive cell ratio increased in EAE group on day 7,14,21 (19.13 ± 2. 53,50. 50 ±8.07 and 33.50 ±6. 16 respectively). NF-κB P65 positive cell ratio of DXM group were 13. 12 ± 1.72,28. 55 ±2. 49 and 18. 00 ±3. 30 on day 7,14,21 respectively,and those of BAC group were 14.00 ± 1.51,32.75 ±3.45 and 17. 37 ±2.44,and there were significant difference as compared with those of EAE group (P＜0.05). (4)The NF-κB P65 mRNA gray scale ratios of EAE group on day 7,14,21 were 0.780 ±0.062,0.980 ±0.105,0.830 ±0.071,which were higher than those of control group (0.550 ±0.065,0.530 ±0.083 and 0.540 ±0.082 respectively). The gray scale ratios in DXM and BAC group were significantly lower as compared with that of EAE group (P＜0.01). Conclusion The results indicate that baicalin preconditioning has neuroprotective effect by suppressing the activation of the NF-κB P65 and reducing the neuron apoptosis.