To explore the influence of Zhibai Dihuang Granule (ZDG) on the anti-inflammatory clotting serum proteins in Yin-deficiency Shanghuo(YDS) syndrome. Yin-deficiency SD rats were induced by intraperitoneal injection of Triiodothyronine (T3). The models of gingivitis in rats were induced by dropwise add of porphyromonas gingivalis model. YDS syndrome rats were treated with ZDG for 1 week. iTRAQ-2DLC-MS/MS was used in screening and identifying the serum differential proteins. With the treatment of ZDG, the serum level of Gelsolin (Gsn), Plasminogen (Plg), Fibnnogenalpha chain (Fga), and Thymus beta-4 (T-β4) were significantly increased (fold change>1.25), while the serum level of Collagulation factor XIII Achain and Colla2 were significantly decreased (fold change<0.8). Gsn possesses the function of removing damaged tissue, releasing the actin, inhibiting the apoptosis of the cells, and inhibiting the apoptosis of the cells. Colla2 and Plgcan regulated the change of blood rheology in the inflammatory site. Gsn and T-beta 4 presented the ability in regulating inflammatory cytokines to promote the healing of inflammatory damage. Conclusion:ZDG may play an important role in clearing actin and lipopolysaccharide released by damage tissue and inhibiting the cell apoptosis. Besides, ZDG may regulate inflammatory factors, change the blood rheology of the inflammatory site, promot the healing of inflammatory damage. In short, ZDG treats YDH syndrome by regulating these proteins associated with anti-inflammatory and clotting.