Simvastatin has important immune-modulatory and anti-inflammatory effects independent of lipid lowering effects. Therefore, our study was conducted to investigate the anti-inflammatory effects of simvastatin either alone or in combination with aspirin. Air pouch granuloma model was used for induction of inflammation in 72 male Wistar albino rats, which were treated with simvastatin (20 mg/kg/day), aspirin (25 mg/kg/day) or both for 3 or 6 executive days. Inflammatory exudates were collected and measured. Oxidative stress was assessed by measuring exudates' malondialdehyde (MDA) and nitric oxide (NO). Inflammatory mediator C-reactive protein (CRP) was investigated using slide agglutination test. Exudates' levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-4 were measured by ELISA. We found that simvastatin alone or in combination with aspirin exerts anti-inflammatory effects by reducing volume of exudates. Simvastatin significantly reduced serum level of CRP and exudates levels of TNF-α, IL-6 and MDA as well as significantly elevated exudates level of NO and IL-4. The results of simvastain were comparable to those of aspirin. In conclusion, air pouch granuloma interrupted the balance between inflammatory and anti-inflammatory markers, which is restored by simvastatin. The anti-inflammatory effects of simvastatin are comparable to aspirin and their combination may produce better effects especially in the attenuation of the oxidative stress and IL-6.