Abstract：Objective：To observe the therapeutic effect of Compound Paishi Decoction on calcium oxalate kidney stone model rats，and to explore its possible mechanism. Methods：A total of 42 male SD rats were randomly divided into six groups：the normal control group，the model control group，the positive control group，the low-，mediumand high-dose groups （0.26 g·mL-1， 0.52 g·mL-1， 1.03 g·mL-1） of Compound Paishi Decoction. The experimental model SD rats with calcium oxalate kidney stone were induced by ethylene glycol and ammonium chloride reagent，and the models were simultaneously treated with low- ， medium- and high-doses of Compound Paishi Decoction by continuous instillation for 28 days. During the experiment， the body weight and other general signs of rats were observed，and the contents of blood urea nitrogen （BUN），creatinine （SCr） and blood calcium （Ca2+） in serum，and urea nitrogen and creatinine in urine as well as the pathological changes of renal tissue were detected. The activation of p38 MAPK signaling pathway [p38 phosphorylation degree （p-p38/p38）， transforming growth factor-β1（ TGF-β1）， P47-phox levels] in renal tissue were evaluated. Results：After four weeks，serum SCr and BUN levels in the model control group were increased when compared with those in the normal control group （P＜0.05）. Compared with those in the model control group， serum SCr and BUN levels in the positive control group were significantly decreased after potassium citrate treatment （P＜0.05）；serum SCr and BUN levels in the medium-dose group and the high-dose group of Compound Paishi Decoction were significantly decreased （P＜0.05），and serum SCr and BUN levels in the low-dose Compound Paishi Decoction group were decreased，but there was no significant difference（ P＞0.05）. After four weeks， the contents of urinary Ca2+ and urinary oxalate in the model control group were increased when compared with those in the normal control group （P＜0.05）， but the concentration of blood Ca2+ was not significantly changed （P＞0.05）. Compared with those in the model control group，the contents of urine Ca2+ and urinary oxalate in the positive control group were decreased （P＜0.05）；the contents of urinary Ca2+ and urinary oxalate in the medium-dose group and the high-dose group of Compound Paishi Decoction were decreased （P＜0.05），and the contents of urinary oxalate in the low-dose group were decreased （P＜0.05）. After four weeks，the NEUT ratio in peripheral blood of rats in the model control group was increased when compared with that in the normal control group （P＜0.05），and the LYMPH ratio was decreased when compared with that in the normal control group （P＜0.05）. Compared with that in the model control group， the NEUT ratio in the positive control group was decreased （P＜0.05）， and the LYMPH ratio was increased （P＜0.05）. The NEUT ratio in the medium-dose group and high-dose group of Compound Paishi Decoction was respectively decreased （P＜0.05） and the LYMPH ratio was increased （P＜0.05）. The levels of p-p38 /p38， TGF-β1 and P47-phox in kidney tissue in the model control group were increased when compared with those in the normal control group （P＜0.05）. Compared with those in the model control group，the levels of p-p38 /p38，TGF-β1 and P47-phox in kidney tissue in the positive control group and the high-dose group of Compound Paishi Decoction were decreased （P＜0.05）. Only P47-phox level in the medium-dose group of Compound Paishi Decoction was decreased（ P＜0.05），and only TGF-β1 level in the low-dose group of Compound Paishi Decoction was decreased（ P＜ 0.05）. According to the observation under microscope，calcium oxalate crystals formed obviously in kidney tissue of rats in the model control group， but less calcium oxalate crystals formed in the positive control group and the Compound Paishi Decoction groups. Conclusion： Compound Paishi Decoction has a good protective effect on calcium oxalate kidney stone model rats，and its mechanism may be related to inhibiting the phosphorylation of p38 in MAPK pathway.