The current study was designed to evaluate the anti-inflammatory effect of GKB in the rat model of granulomatous inflammation. Thirty rats were distributed into five groups:  The first group served as negative control group that received distilled water (DW) only without inducting inflammation, positive control group; treated with DW with the induction of inflammation and they were assigned to cotton pellet-induced granuloma, ginkgo biloba (GKB) treated group (200mg/kg/day), dexamethasone-treated group (1mg/kg), and Prednisolone treated group (5mg/kg). All the treatments were given orally for seven consecutive days.  On day eight, the rats were anesthetized and the pellets together with granulation tissue were carefully removed and made free from extraneous tissue. The weight and the percent of the exudate and granuloma were determined and samples of the tissues were sent for histopathological examination. Blood samples were collected by cardiac puncture and used for the analysis of the inflammatory markers: TNF-alfa, IL10, VCAM-1, and hs-CRP. The study revealed a significant reduction in the weight and the percent of exudate (p-value = 0.019), (17%) and granuloma (p-value = 0.013), (20%) by GKB which was comparable to that produced by prednisolone. All the treatment groups showed a significant reduction in serum TNF-?, VCAM-1, and hs-CRP concentration compared with the positive control. The histopathological finding revealed pronounced improvement. In the current study, GKB was effective in attenuating the level of inflammation by decreasing the exudate, granuloma, and inflammatory markers. The underlying mechanisms could be the inhibitory effect on the expression of the inflammatory cytokines and endothelial adhesion molecule. These findings suggest GKB as a good contender to be tested in the treatment of inflammatory diseases.