Mounting evidence shows that adiposity is closely related to elevated blood pressure (BP); however, the underlying mechanism of this relationship is not clearly understood. We aimed to assess the mediating effects of an inflammatory factor (high sensitivity C-reactive protein, hsCRP) and adipokines, as well as any sex differences, on the relationship between adiposity and BP among Chinese overweight or obese adults. A total of 1221 overweight or obese subjects aged 20-55 years who lived in Beijing for at least 1 year were recruited in 2014. The percentage of body fat (PBF) was examined using dual energy X-ray absorptiometry (DXA). Mediation analyses were conducted to examine the mediation of hsCRP, leptin, and adiponectin on the relationship between adiposity and BP by sex. Serum hsCRP and leptin levels were positively associated with PBF (P < 0.001) in males and females. Adiponectin and leptin levels were associated with systolic BP (SBP), but only in males, while in females, the hsCRP level was associated with SBP and diastolic BP (DBP). In males, leptin mediated 22.5% of the relationship between adiposity and SBP and 31.4% for DBP (mediation effect = 0.059 and 0.068, respectively, P < 0.05). However, in females, hsCRP mediated 30.2% of the relationship between adiposity and SBP and 29.5% for DBP (mediation effect = 0.058 and 0.063, respectively, P < 0.001). There are sex differences in the mediation roles of hsCRP and adipokines on the relationship between adiposity and BP. Leptin mediated part of the relationship between adiposity and BP in males, while hsCRP mediated the relationship in females. Our results provide evidence for adiposity-related high BP control measures in a sex-specific manner and provide hints for exploring the potential mechanisms of obesity-related hypertension.