Reduced inflammation is one of the potential mechanisms underlying the cardioprotective efficacy of fish oil enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Supplementation with fish oil has favorable effects on cardiometabolic profiles in Inner Mongolia patients with hypertension, but whether the cardiovascular benefits can be ascribed to reduced subclinical inflammation is unclear among this population. Seventy-seven middle-aged/elderly hypertensive volunteers were randomly assigned to receive either fish oil (FO, n = 38, 2 g day-1 EPA + DHA) or control corn oil (CO, n = 39) for 90 days. FA compositions in erythrocytes and C-reactive protein (CRP, mg L-1), interleukin-6 (IL-6, pg mL-1) and tumor necrosis factor-α (TNF-α, pg mL-1) concentrations in the plasma were measured before and after the 90-day supplementation, and the cardiometabolic risk was expressed as continuously distributed z-scores calculated by standardizing and then summing the individual cardiovascular risk factors. Significant reductions in the TNF-α (-1.87 ± 2.71 vs. -0.64 ± 2.62, p = 0.02) and CRP levels (-0.85 ± 2.49 vs. 0.56 ± 2.14, p = 0.01) were found in the FO group compared with the CO group, but not in the IL-6 levels (-0.66 ± 1.05 vs. -0.25 ± 0.94, p = 0.10). The decreases in the changes of TNF-α levels were positively correlated with the reductions in the cardiometabolic risk scores in the subjects supplemented with FO (r = 0.35, p = 0.02), but not in the control subjects supplemented with CO (r = 0.09, p = 0.54). FO supplementation increased the levels of EPA (p = 0.013), DHA (p = 0.040) and total n-3 FA (p = 0.035), and decreased the levels of 20:4n-6 (p = 0.041) and total n-6 FA (p = 0.011) and the ratio of n-6 to n-3 FA (p = 0.001), compared with the changes related to the CO group. The increases in the changes of erythrocyte total n-3 FA levels were inversely correlated with the concentrations of TNF-α (r = -0.34, p = 0.001) and CRP (r = -0.29, p = 0.020). The present findings suggest that fish oil supplementation may attenuate the proinflammatory reactions in hypertension, which might help promote the cardiometabolic benefits in this Inner Mongolia population.