Amyotrophic lateral sclerosis (ALS) is a chronic neuromuscular disorder reflecting a progressive degeneration of motor-neurons. Despite numerous studies about ALS pathogenesis, significant achievements in understanding and treating this disease are still lacking. Mesenchymal stem cells (MSCs) are stromal cells obtained from the bone marrow that could provide a cell source for repair of injured tissues. MSCs have been shown to be effective in several experimental models of neurological diseases. Metallothioneins (MTs) are a class of low-molecular weight metal-binding proteins involved in scavenging of free radicals, storage and metabolism of essential metals and detoxification of toxic metals. The present study was aimed at evaluating the expression of three MT isoforms (MT-1, MT-2 and MT-3) and the level of oxidative stress in spinal cord of SOD1/G93A(+) mice, a transgenic model for ALS. Moreover, the effects of the intravenous injection of MSCs in SOD1/G93A(+) mice during the symptomatic stage of disease were assessed. Expression of all MT isoforms was increased in SOD1/G93A(+) mice with respect to controls, as well as the activity of the anti-oxidant enzyme glutathione S-transferase (GST). Interestingly, MSC administration turned around the increase in mRNA expression of MTs and in activity of GST. Our results demonstrate that ALS progression is associated with development of oxidative stress conditions in the spinal cord, and that treatment with MSCs significantly reduces both MT up-regulation and the increased GST activity accompanying the progression of the disease.