Mesenchymal stem cells (MSCs) exert their effects in part by limiting oxidative stress. Of therapeutic interest are the effects of MSCs in obesity, a cause of elevated reactive oxygen species (ROS). ROS are particularly deleterious as they are associated with decreased insulin sensitivity and low-grade inflammation. The current study analyzed the antioxidant activity of MSCs in the dietary-induced obese C57BL/6 model. The hypothesis was that MSCs would modulate increases in ROS production associated with dietary-induced obesity. Acute treatment of obese, insulin resistant animals normalised hepatic oxidative stress. Interestingly, MSC-treatment had no effect on insulin resistance, glucose tolerance and low-grade inflammation – conditions associated with ROS. The current study is the first to ascertain the potential use of MSCs to curb diet induced oxidative stress. Results provoke further exploration into the specific mechanisms by which MSCs reduce ROS in insulin resistant pathology.