Abstract: Objective To observe the expression of HSPB8 in spinal cord tissues of spontaneous type 2 diabetes db/db mice, and explore the neuroprotective mechanism of HSPB8. Methods Eight weeks old, male, db/m mouse(db/m group, 10 mice), db/db mouse(db/db group, 10 mice) were selectd. Body weight and fasting blood glucose were dynamical observation. HE staining was used to observe spinal cord in mice. mRNA expressions of HSPB8, Caspase-1, IL-18, P62 and LC3 were detected by qRT-PCR. For the in vitro model of diabetes, RGC-5 cells were stimulated with glucose concentrations of 11, 25, 30 and 35 mmol/L for 48 hours, respectively. RGC-5 cells were silenced by HSPB8 protein and stimulated by high glucose(35 mmol/L) for 48 h. HSPB8, Caspase-1, IL-18, P62 and LC3 were detected by western blot. Group t-test and one-way ANOVA were used for comparison between groups. Results (1)HE staining results showed that spinal cord tissue of db/db mice was damaged;(2)qRT-PCR results showed that HSPB8, Caspase-1, IL-18, P62 and LC3 were expressed in diabetic spinal cord tissues;(3)Western blotting results showed that compared with the db/m group of mice, the db/db mice were damaged spinal cord tissues HSPB8, LC3-Ⅱexpression were decreased, and the Caspase 1, IL-18, P62 expression were increased(all P<0.05). With the increase of blood glucose concentration, the expression of HspB8, LC3-Ⅱwere decreased, and the caspase-1, IL-18 and p62 were increased(all P<0.05);(4)Forty-eight hours after RGC-5 cells HSPB8 silence sugar stimulation, the Caspase 1, IL-18 and P62 protein expression were increased and LC3-Ⅱexpression were declined(all P<0.05). Conclusion HSPB8 plays an important protective role in diabetic neuropathy, and its mechanism may be related to the effect of HSPB8 on inflammatory factors and autophagy in neurons.