Sirt1, a member of class III nicotinamide adenine dinucleotide (NAD+)- dependent deacetylases, is involved in regulating adaptive pathways to cellular stress cues such as calorie restriction and is strongly linked to improving health and lifespan . Overexpression of Sirt1 is known to increase metabolic efficiency in numerous organisms including yeast worms, flies and rodents. Here we show data from a SIRT1 transgenic mouse line that constitutively overexpress elevated levels (>x5) of SIRT1 compared to lower levels (1.5-2 fold) in previously described transgenic mice. While mitochondrial function has been previously reported to increase in response to the overexpression of SIRT1, in this study, we show that this may be mediated through an overall increase in complex IV of the respiratory chain mediated respiration. These transgenic mice also display phenotypes similar to calorie restriction, performing better on several metabolic parameters, including better glucose tolerance, lower insulin levels, and are more insulin sensitive. They also display a lower body weight and fat mass compared to wild type littermates. These findings have important implications in offering opportunities for therapeutic interventions in several diseases such as type II diabetes.