The interaction between intracellular magnesium level, adiponectin production and insulin sensitivity has been recently suggested in both diabetic patients and their first-degree relatives. The present study aimed to investigate whether magnesium supplements are able to increase plasma adiponectin and af-fect insulin sensitivity in first-degree relatives of subjects with type 2 diabetes. Seventy subjects who were first-degree relatives of diabetic patients were randomly allocated to either Mg hydroxide supplementation plus lifestyle (case group, n= 35) or mere lifestyle change and placebo (control group, n= 35). The subjects were seen at 16-weeks intervals for at least 24 months. There was no difference in baseline level of adiponectin between intervention and control group (p= 0.612), but significantly increased in intervention group (mean change of 6.51 ± 4.33 mg/dl, p≤ 0.001) and significantly reduced in control group (0.70±0.52 mg/dl, p≤ 0.001) after 16-week intervention protocol. No difference was revealed in initial insulin resistance between the two study groups (p= 0.527), but it was revealed lower in intervention group after completing treatment (p≤ 0.001). On the other hand, after 16 week of initial interventions, insulin resistance index reduced as 0.56±0.85 units (p≤ 0.001), while increased in control group as 0.68 ± 0.78 units (p≤ 0.001). The increase in adiponectin production as well as decrease in insulin resistance is expected by administrating magnesium supplements in first-degree relatives of the patients with diabetes mellitus.