Diabetes is a metabolic disease characterized by hyperglycemia and insulin resistance. Curcumin is a potential antidiabetic agent regulates gene expression and different signaling pathways. The present study determined the effect of curcumin on AMPK, PPARγ, SIRT1 and NF-κB expression in liver of a diabetic mice. Four groups of mice (n = 3) were used: wild type (WT), diabetics (db/db) and WT and db/db treated with Curcumin 0.75% (WT+C and db/db+C, respectively) administered in the diet for 8 weeks. Protein expression was determined by Western blot. Curcumin prevented partially the weight loss in db/db mice, increased AMPK and PPARγ expression and diminished NF-κB protein in db/db mice, but did not alter the SIRT1 expression. Curcumin regulates AMPK, PPARγ and NF-κB expression, but not of SIRT1.