OBJECTIVE： To study the effects of curcumin on the expression of tumor suppressor gene p53， E3 ligase Siah-1 and cognitive associated protein Synaptophysin in glioma cells C6 of rats cultured in high glucose. METHODS： CCK-8 assay was used to detect survival rate of C6 cells after treated with 10， 20， 30， 40， 50， 60， 70， 80， 90， 100 μmol/L curcumin for 24， 48 h under high glucose environment. Western blot method and RT-PCR method were adopted to detect the protein and mRNA expressions of p53， Siah-1 and Synaptophysin in C6 cells of normal control group （without any treatment）， high glucose treatment group， curcumin low-concentration and high-concentration groups （high glucose+10， 30 μmol/L curcumin） after cultured for 24 h. Same method was used to determine the effects of P53 gene of C6 cells on protein and mRNA expression of Siah-1 after transfected with siRNA under high glucose environment. RESULTS： Curcumin had no significant effect on the survival rate of C6 cells in the range of 10-40 μmol/L. The survival rate of C6 cells decreased significantly in a concentration-dependent manner when the concentration of curcumin was higher than 40 μmol/L. Compared with normal control group， the protein and mRNA expressions of p53 and Siah-1 in C6 cells were enhanced in high glucose treatment group， while the protein and mRNA expressions of Synaptophysin were decreased， with statistical significance （P＜0.05）. Compared with high glucose treatment group， the protein and mRNA expressions of p53 and Siah-1 in C6 cells were decreased in curcumin low-concentration and high-concentration groups， while the protein and mRNA expressions of Synaptophysin were enhanced， with statistical significance （P＜0.05）. Under treated with high glucose， the protein and mRNA expressions of Siah-1 in C6 cells were decreased significantly after silencing p53 gene （P＜0.05）. CONCLUSIONS： Under high glucose environment， curcumin can up-regulate the expression of Synaptophysin in C6 cells by down-regulating the expression of p53 and Siah-1.