The present study investigate the effect of ascorbic acid, the major bioactive component isolated from Cissus quadrangularis extract (CAA) on inflammatory cytokines and growth factors in non-steroidal anti-inflammatory drug (NSAID) induced gastric ulcer. Analysis of serum cytokine profile using enzymelinked immunosorbent assay (ELISA) showed a drastic increase in interleukin (IL)-1β, IL-6, tumour necrosis factor-alpha (TNF)-α, interferon-gamma (IFN-γ) and decrease in IL-10, Il-4 and prostaglandin E2 (PGE2) levels in NSAID (aspirin) treated rats. The reduction of growth factors such as transforming growth factor-alpha (TGF)-α and vascular endothelial cell growth factor (VEGF) by aspirin was determined by immunohistochemistry method. Administration of CAA produced significant protection against aspirin induced gastric toxicity by showing significant increase in PGE2, TGF-α, VEGF expression and accompanied by a significant inhibition of nitric oxide and regulating the levels of cytokines in rats. These findings suggest that CAA prevents gastric ulcer formation due to its immunomodulatory effect, antioxidant activity along with the ability to modulate PG synthesis and up-regulation of the growth factors.