Whether the decrease of insulin action is a biological consequence of age or a result of lifestyle changes in elderly people is uncertain. Therefore, we rigorously controlled potential confounders to evaluate the relationship between age and insulin resistance in Mexican women. A total of 100 glucose-tolerant, non-hypertensive women, 30-65 yr of age, inhabitants of the same neighborhood of Durango, a city in the North of Mexico, were randomly enrolled to participate in a case-control study. The study was designed to include 50 cases and 50 controls. Insulin-resistant women were considered as cases and compared vs a control group of non-insulin resistant women, matched by BMI and Waist-to-Hip ratio (WHR). HOMA-IR index equal or greater than 3.0 defined the presence of insulin resistance. Endocrine diseases, pregnancy, smoking, alcohol consumption, and physical activity were exclusion criteria. The results showed insulin resistant women were significantly older than control women (53.7 +/- 12.2 vs 46.3 +/- 10.4, p = 0.0004). Women in the case group showed a direct correlation between age and HOMA-IR index (0.427, p = 0.02), whereas control women did not (0.09, p = 0.626). Step-wise forward selection logistic regression analysis showed an independent relationship between HOMA-IR index and age (OR 1.5, CI95% 1.4-1.8, p = 0.002). The results of this study show an independent relationship between age and high HOMA-IR index in Mexican women, supporting the hypothesis that age per se could be associated with the impairment of insulin action.