Rationale: Obesity is a growing public health problem due to its significant morbidity andmortality with chronic subclinical metabolic inflammation, cardiovascular diseases and low quality oflife. Its control is still far from satisfactory. Objective: We aimed at exploring some possible mechanisms(inflammatory mediators and adipokines) for the potential preventive and therapeutic effects oforal olive oil supplementation against high fat diet (HFD)-induced metabolic inflammation and obesityin rat model. Animals and Methods: We randomly grouped young adult male Wister Albino ratsinto 5 groups (n = 10 each) to receive: Group I - a standard diet, Group II - a standard diet + oralolive oil (OO; 1.3 mL/kg, b.w.), Group III - HFD, and, Groups IV/V - a HFD + OO in preventive (16weeks)/therapeutic (4 weeks) manner for at total of 16 weeks. Lipid profile and apolipoproteins (TC,TG, LDL-C, HDL-C, VLDL-C, ApoA1, and ApoB), adipokines and proinflammatory cytokines (IL-6,TNF-α, CRP and MCP-1, leptin, resistin, RBP-4, and visfatin) were quantitatively measured in serum.Statistical analysis was done with SPSS for Windows version 17.0. Results: In Group II, significantlyhigher serum levels of leptin, resistin, RBP-4, visfatin compared to each of Groups I or III. SerumIL-6, TNF-α and MCP-1 levels were significantly increased in Group II obese rats as compared toGroup I, whereas, Groups IV and V rats showed significant decrease in pro-inflammatory cytokines.Serum adiponectin in Group II were significantly lower than each of Groups I or II, but was significantlyincreased in Groups IV and V rats. Serum HDL-C was significantly increased in Groups IV andV rats vs. Group II. Serum Apo-A1 was increased significantly in Groups IV and V as compared toGroup II, while serum Apo-B was significantly decreased. Conclusion: Study results provide a supportto the anti-obesity effect of olive oil in both preventive and therapeutic manners, although theformer was more efficient. It acted through modulating each of the beneficial adipokines and thepathogenetic proinflammatory cytokines as reflected on body weight gain and serum lipogram. Howsuch effects at the molecular level happened necessitates further investigations