We conducted a comprehensive and in-depth assessment of body mass index (BMI) or waist circumference (WC) related to blood pressure (BP) and determined whether the association is mediated by the possible potential mediators in the cross-sectional survey of the Harbin Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases of 7094 participants aged 20-74 years, and validated the significant findings in the US National Health and Nutrition Examination Survey four cross-sectional cohorts (2005-2006, 2007-2008, 2009-2010, and 2011-2012) and the cohort data of the Harbin People's Health Study (a median of 4.2 follow-up years). We observed that BMI or WC was positively associated with BP (all P-values < 0.0001). Mediation analyses consistently indicated that these associations were mediated mainly by insulin resistance (IR) as measured by the homeostasis model (HOMA-IR), followed by triglyceride (TG) and total cholesterol (TC), and fasting glucose (FG) in the three studies. The proportions via the mediation of insulin/HOMA-IR were 25~40%, TG and TC were 15~20%, and FG was 2~8%, respectively. These findings suggest that the mediators, insulin/insulin resistance, TG, TC, and FG, could be targeted for preventing hypertension among populations who were overweight or obesity.