ArtículoBackground: In type 2 diabetic mouse liver, hyperglycemia, and insulin modify gene expression. Curcumin is a powerful antioxidant and antidiabetic agent that regulates the gene expression of different signaling pathways through various transcription factors. Therefore, we hypothesized that curcumin modifies the protein expression profile in the liver of diabetic db/db mice. Objective: To determine the effects of curcumin on the liver protein profile of diabetic db/db mice. Methods: db/db and Wild Type (WT) male mice were allocated in four groups, and they were fed for eight weeks. Three WT and three diabetic db/db mice received a Standard Diet (SD; WT and db/db groups, respectively); three WT and three diabetic db/db mice received a SD supplemented with 0.75% (w/w) curcumin (WT+C and db/db+C groups, respectively). Liver proteins were separated by 2D electrophoresis. Differential protein expression analysis was performed on Image- Master 2D Platinum software, and selected proteins were identified by MALDI-TOF-MS and subjected to enrichment analysis using STRING and DAVID databases. Results: Thirty-six proteins with differential expression due to diabetic background and curcumin treatment were found; these proteins participate in the metabolism of amino acids, carbohydrates, and lipids. Interestingly, the altered expression of seven proteins was prevented in the liver of the diabetic mice that received curcumin. Conclusion: Among all differentially expressed proteins, curcumin reverted the altered expression of seven proteins. Thus, although it was observed that curcumin did not affect the biochemical parameters, it does modify the expression of some liver proteins in diabetic mice.