objective To discuss Bupivacaine act on SH-SY5Y cells in high sugar environment increasing ROS and apoptosis . Methods we adopt 1mmol/L bupivicaine to SH-SY5Y cells cultured by different concentrations of glucose medium ,and employ flow cytometry to detect the quantity of ROS in the cells and the situation of apoptosis.we use MTT method to detect cell survival rate .At last we use Western blotting technique to detect the change of the related protein about GRP78. Measurement data were presented as mean±standard deviation. SPSS 13.0 software was used for statistical treatment. The quantity of ROS and the situation of apotosis and cell survival rate and the quantity of GRP78 were analyzed by one-way ANOVA and comparisons among groups were made by LSD (homogeneous variance) or Dunnett’s T3 (heterogeneity of variance). P < 0.05 was considered statistically significant . Results The quantity of ROS in the cells cultured by glucose medium increasing gradually and the apoptosis and cell survival rate have statistical differences（P<0.01）.Western blot results show that GRP78 express enhance in endoplasmic reticulum stress. Conclusion Intracellular ROS increasing and apoptosis are associated with Bupivacaine further strengthening endoplasmic reticulum stress. Endoplasmic reticulum stress cause ROS outbreak in cells, leading to cell damage and apoptosis. With the function of GRP78 degrading, endoplasmic reticulum stress further strengthen.