The relationship between insulin resistance (IR) and essential hypertension (HTN) is controversial. The aim of this study was to determine the association of IR estimated by homeostasis model assessment of insulin resistance (HOMA-IR) and HTN in a large sample of Iranian diabetic and non-diabetic population. A total of 2047 diabetic and non-diabetic individuals with or without HTN, aged 30-75 yrs, who were referred to a university general hospital between November 2004 and April 2007 were included in this study. Demographic data and anthropometric characteristics of participants were recorded. Fasting blood samples were collected, and fasting plasma glucose (FPG), serum creatinine, lipids, insulin, C-peptide and HbA1c were measured. HOMA-IR and HOMA derived Beta-cell function (HOMA-B) were also calculated. Age, sex and waist girth adjusted HOMA-IR values were compared between hypertensive and normotensive subjects. Hypertensive patients had significantly higher HOMA-IR than age-, sex-, and waist girth-adjusted normotensive individuals in both non-diabetic (2.163 +/- 0.08 and 1.75 +/- 0.03, p < 0.001) and diabetic (3.40 +/- 0.10 and 3.07 +/- 0.09, p < 0.05) groups. Multivariate logistic regression analysis showed that after adjustment for age, sex, waist girth, BMI, triglyceride, total cholesterol, FPG, and C-peptide, HOMA-IR was a significant independent predictor of HTN in all subjects (odds ratio = 1.117, CI 95% = 1.026-1.216, p < 0.05) and in diabetic and non-diabetic subjects separately (odds ratio = 1.102, CI 95% = 1.009-1.203, p < 0.05 and odds ratio = 1.328, CI 95% = 1.116-1.580, p < 0.01, respectively). In conclusion, this study showed that IR is associated with HTN in Iranian diabetic and non-diabetic subjects.