Many investigators suggest that insulin resistance of the peripheral tissues is the primary defect that results in non-insulin dependent diabetes mellitus (NIDDM). It is also generally accepted that multifactorial controls, playing in concert for gene expression trigger this disease. Previous research reports indicated that uric acid metabolism plays a role in the pathogenesis of NIDDM. To investigate this hypothesis, we studied 53 NIDDM patients by using a double blind cross over control study, of allopurinol and placebo administration. We found a statistically significant elevation in the level of hemoglobin A1c (HbA1c) after the allopurinol intervention period of 12 weeks compared with the placebo period of the same duration (p less than 0.003). The elevation was also found in a subgroup with Body Mass Index (BMI) less than 25 kg/m2 (p less than 0.001) and BMI more than or equal to 25 kg/m2 (p less than 0.05). No statistically significant differences between fasting plasma glucose, glucose tolerance test, serum insulin, total cholesterol, triglycerides, high density lipoprotein cholesterol, creatinine, prior to and after use of allopurinol were noted except for serum uric acid (p less than 0.001). No relationship between changes in HbA1c and changes in uric acid, analysed by linear regression analysis and correlation was demonstrated (r = 0.15, p = 0.29). We conclude that the changing of hemoglobin A1c may be a direct effect of allopurinol or support the role of uric acid in the pathogenesis of NIDDM.