Abstract: To investigate the effects of curcumin on mitochondrial dysfunction induced by high glucose(40 mmol/L glucose, 24 h)in L6 cells, curcumin(10, 20, 40 μmol/L)was administered for 24 h after high glucose culture. The effects of curcumin on the mitochondrial dysfunction were evaluated by mitochondrial membrane potential, reactive oxygen species(ROS), ATP content and mtDNA copy number. The mRNA and protein expression of uncoupling protein 2(UCP2), PPARγ coactivator 1α(PGC-1α)and sirtuin-1(Sirt3)were also determined. As improvement of high glucose damage, curcumin significantly raised mitochondrial membrane potential and ATP content, and decreased ROS level. Curcumin significantly ameliorated the down regulation of UCP2 yet with little effect on mtDNA copy number and PGC-1α and Sirt3 expression. In conclusion, curcumin could significantly ameliorate mitochondrial dysfunction in L6 cells induced by high glucose, which involved the mechanism of multiple antioxidants.