Purpose: This study was aimed to evaluate the antioxidant and anti-inflammatory effects of vitamin D and Simvastatin (SIM) on a high-fat diet (HFD) induced-obese rats. Methods: 40 adult male rats were divided into four groups: control group, HFD, HFD + vitamin D, and HFD + SIM for 14 weeks. Vitamin D or SIM supplementation was done for the last 6 weeks. Vitamin D dosage was 500 IU/kg, while SIM dosage was 10 mg/kg. Interleukin-6 (IL-6) concentration and markers of oxidative stress including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced glutathione(GSH) concentrations in serum were determined using ELISA kits and spectrophotometry methods, respectively. Results: Treatment with vitamin D or SIM could significantly reduce IL-6 and MDA and increases SOD, GPx activities, and GSH levels. Oxidative stress can result not only from increased ROS production but also from dysfunctional antioxidant defenses. Conclusion: From the experimental results, it was observed that SIM and vitamin D could attenuate oxidative stress and inflammation markers associated with obesity.