Although obesity and insulin levels are generally associated in cross-sectional data, the temporal and causal nature of their association is not yet clear. Increased obesity may have preceded increased insulin levels or vice versa. The authors examined the temporal relations between fasting insulin blood levels and weight in longitudinal data from the ongoing Normative Aging Study. Two insulin measurements from which a rate of change (delta Insulin) could be calculated were available from 376 non-diabetic male subjects (mean age = 62.1 years). Rate of change in weight could be calculated for the previous inter-examination period (delta Weight1), the contemporaneous period (delta Weight2), and the inter-examination period following the second insulin measurement (delta Weight3). delta Weight2 was a significant predictor (p = 0.0005) of delta insulin in multiple linear regression models that included control for potential confounders (body mass index, waist-to-hip ratio, antihypertensive and diuretic medication use, and age) and for correlation between the initial level and change in insulin (mean fasting insulin). delta Weight1 was added to the model and was found not to be statistically significant (p = 0.15). When the model was stratified by age tertile, the regression coefficient on delta Weight1 was -0.44 (p = 0.018) for the youngest stratum, -0.06 (p = 0.72) for the middle stratum, and 0.21 (p = 0.19) for the oldest men. Similarly, delta Insulin was a significant predictor of delta Weight3 (p = 0.026) in a separate regression model. These findings are consistent with both possible temporal sequences of association between changes in insulin and obesity. The intricate homeostatic mechanisms that regulate changes in insulin and obesity may not be readily amenable to description in terms of cause and effect.