Objective-To test the potential anti-oxidant and anti-inflammatory effects of febuxostat and/or stopping high-fat diet on the biochemical parameters of high fat diet-induced hyperlipidemic rabbits.Background-Febuxostat, a highly potent xanthine oxidase inhibitor with antioxidant effect, inhibits elevated xanthine oxidase, leading to reduction of reactive oxygen species (ROS) and oxidative stress, the main causes of vascular inflammation in hyperlipidemia. Methods-Male NewZealand rabbits were distributed in three groups: normal control (NC) fed standard chow for 12 weeks; the other two groups fed high-fat diet (HFD) with 1% cholesterol for 8 weeks, and then shifted to standard chow for 4 weeks. During the last 4 weeks; the (HFD) group received vehicle 0.5% carboxymethyl cellulose (CMC), while the treated (FX) group received febuxostat in doses (2 mg/kg/day p.o.). Results-Febuxostatsignificantly lowered "bad" cholesterol. Febuxostat also displayed a potent anti-inflammatory and antioxidant activity by decreasing serum levels of lipid peroxidation index, pro-inflammatory cytokines and enhancing antioxidant-enzyme activity. Stopping hyperlipidemic diet in HFD group didn't show improvement. Conclusions-These findings indicate antioxidant and anti-inflammatory effects of febuxostat that may be common mechanisms of the anti-hyperlipidemic effect of this drug. Stopping hyperlipidemic diet without treatment is not sufficient once injury occurred.