Objective To observe the effect of Kouyanqing granule on oral ulcer in the model rats with yin deficiency, and to investigate mechanism of the nourishing-yin effect of Kouyanqing granule. Methods The ratswere randomly divided into normal control group, model group, Zhi Bai Dihuang pills group (1.08g·kg-1), and the high, medium and low dose of Kouyanqing granule groups (8, 4, 2g·kg-1). Thyroxine and Na OH were usedto induce the oral ulcer model rats with yin deficiency. The symptoms of yin deficiency including weight, waterintake, body temperature, and cAMP, cGMP, cAMP/cGMP in blood plasma, as well as Na+-K+-ATP enzymeactivity in erythrocyte membrane were measured. The effect of Kouyanqing on the degree of ulceration in model rats was observed TNF-α, IL-6, IL-10, EGF, TGF-β1 contents in oral mucosa were measured by ELISA, andexpression of p38MAPK in oral mucosa was also detected by Western Blot. Results Compared with the normal control group, rats in model group showed significant decrease in weight, and increase in water intake and body temperature (P<0.05, P<0.01). The score of ulcer repairement were reduced obviously (P<0.01). The model group also showed significant increase in cAMP, cAMP/cGMP in blood plasma (P<0.01), Na+-K+-ATP enzyme activity in erythrocyte membrane (P<0.01), TNF-α, IL-6 levels in oral mucosa (P<0.05), and the expression of p38 MAPK (P<0.05). The levels of cGMP in blood plasma (P<0.05) and IL-10, EGF, TGF-β1 in oral mucosa (P<0.05, P<0.01) were decreased obviously in model group. Compared with the model group, the highand medium dose of Kouyanqing granule showed significant increase in weight (P<0.05, P<0.01). Kouyanqing granule could reduce water intake and body temperature (P<0.05, P<0.01), and increase the score of ulcer repaire (P<0.05, P<0.01) obviously. The high and medium dose of Kouyanqing granule could reduce cAMP, cAMP/cGMP levels, and Na+-K+-ATP enzyme activity (P<0.05, P<0.01). The level of cGMP was increased obviously (P<0.05) in medium dose group of Kouyanqing granule. At the same time, the high dose of Kouyanqing granule could reduce TNF-α, IL-6 levels in oral mucosa remarkably (P<0.05, P<0.01). The high and medium dose of Kouyanqing granule could increase IL-10, EGF, TGF-β1 levels obviously (P<0.05, P<0.01). The expression of p38MAPK could be reduced by Kouyanqing granule (P<0.05) in a dose-dependent manner. Conclusion Kouyanqing granule could improve the symptoms of yin deficiency. Kouyanqing granule has remarkable effect on oral ulcer with yin deficiency. The role of Kouyanqing granule is related to the nourishing-yin effect via mechanisms which may be associated with mediating the expression of p38MALK to inhibit inflammatory reaction and elevating levels of EGFs.