Insulin is a key regulator of energy metabolism in the body, and it particularly regulates glucose uptake. Insulin resistance is when the body, or certain tissues, have an impaired response to insulin. Often insulin resistance is associated with metabolic disease, but it can also be a normal occurrence, particularly during periods of rapid growth. However, the molecular mechanisms of this ‘physiological’ insulin resistance are not well understood and likely have sex-linked differences. To close this gap, researchers examined the responses to insulin and glucose in 20-day-old rats, as this age is a period of rapid growth near weaning. Both female and male rats had elevated glucose and insulin levels along with low sensitivity to insulin and intolerance to glucose. But there were sex- and tissue-specific differences in the activation of insulin-activated signaling proteins, like S6K1, Akt, and GLUT4. While more research is needed, the information gathered in this study expands our understanding of insulin resistance and can also be used to better understand the impact of sex on harmful types of insulin resistance.