Moreover, oxaliplatin repeated treatment induces severe peripheral neuropathy that can affect approximately 50% of the patients receiving cumulative doses higher than 1000 mg/m2. Anti-hyperalgesic compounds currently used to treat chemotherapy-induced pain, like antiepileptics or antidepressant, are weakly effective. The therapeutic failure reflects the lack of knowledge about the molecular bases of neuropathies. In a rat model of oxaliplatin-induced neuropathy we previously identified oxidative stress as a main biomolecular dysfunction showing a relationship between oxidative damage of the nervous system and pain. The “oxidative hypothesis” was confirmed in primary cultures of astrocytes, a glial cell type activated in vivo by oxaliplatin treatment. Since oxaliplatin does not possess direct oxidative properties, redox unbalance seems due to a cellmediated effect able to alter the oxidative machinery. After oxaliplatin treatment, mitochondria are modified in morphology and impaired in function. Less inquired is the role of the other intracellular organelle strongly implied in redox processes: the peroxisome. Peroxisomes are the last among the subcellular organelles to be identified. The discovery of the co-localization of catalase with H2O2-generating oxidases in peroxisomes was the first indication of their involvement in the metabolism of oxygen metabolites. The high peroxisomal consumption of O2, the demonstration of the production of H2O2, O22 and more recently of ?NO, as well as the discovery of several ROS metabolizing enzymes in peroxisomes has supported the notion that these ubiquitous organelles play a key role in both the production and scavenging of ROS in the cell. In the nervous system, the functional relevance of these organelles is dramatically highlighted by peroxisomal disorders. Severe demyelination, axonal degeneration and neuroinflammation are induced by genetic deficit of peroxisome. Moreover, peroxisomes were recently involved in the development and progression of specific degenerative diseases. In mouse liver was originally CPI-613 cloned a nuclear receptor subfamily of ligand-activated transcription factors, the Peroxisome Proliferator-Activated Receptors . PPARs may activate genes with a PPAR response element in their promoter regions. Girnun et al. highlighted that PPARc stimulation increases the expression and activity of catalase, a heme-containing peroxisomal enzyme that breaks down hydrogen peroxide to water and oxygen. Recently, agonists of the c subtype of PPARs received considerable attention as potential therapeutic agents for a wide range of neurological diseases, including neurodegenerative diseases, traumatic injuries, stroke and demyelinating diseases. Aimed to characterize the oxaliplatin neurotoxicity, we studied the peroxisome-related signal in vitro, in astrocyte cell culture, and in vivo in a rat model. Peroxisome stimulation by the PPARc agonist rosiglitazone was analyzed to individuate new possible pharmacological.