Due to the production of reactive oxygen species (ROS), oxidative stress has been implicated in the pathogenesis of silica-induced lung fibrosis. So it is hypothesized that grape seed extract (GSE) or vitamin E (Vit E) as antioxidants may ameliorate some symptoms of the disease. Male Wistar albino rats were divided into 7 groups: rats in group I instilled intratracheally (IT) with a single dose of silica suspension (50mg/rat) as positive control (PC). Treatment groups (II-IV) received Vit E (20 IU/kg/day), GSE (150 mg/kg/day), or Vit E+GSE simultaneously orally 1 day after instillation of silica. Groups V and VI were given oral GSE or Vit E after instillation of the equivalent volume of saline (IT) as controls for GSE or Vit E. Rats of group VII only instilled saline (IT) as negative control. After 90 days animals were sacrificed and plasma-malondialdehyde (p-MDA) and lung tissue hydroxyproline (HP) were quantified. The lungs were also investigated for histopathological changes. The mean concentrations of p-MDA and HP in studied groups (I-VII) were 1.95, 2.77, 0.72, 0.81, 0.64, 0.94, 1.02 micromolMDA/L(plasma) and 28.476, 27.85, 22.83, 22.64, 15.40, 18.31, 18.51 mgHP/g(tissue), respectively. Silica caused a significant increase in HP content of lungs and MDA levels in the plasma except in GSE-treated groups (III and IV). According to the results of this study GSE could reduce the fibrogenic effect of silica. However; no synergistic effect was observed after co-administration of GSE and Vit E.