Objective To investigate whether Huang Qi-San Qi mixture can be used to treat chronic kidney disease(CKD)rats by improving the structure of the colon mechanical barrier. Methods Thirty male Sprague-Dawley rats were randomly divided into five groups: sham group, model group (I/ R group), low dose of Huang Qi-San Qi mixture group (L-HSM group), high dose of Huang Qi-San Qi mixture group (H-HSM group), and NiaoDuqing group (NDQ group). The model of chronic kidney disease (CKD) was established by right nephrectomy and left kidney ischemia reperfusion. The blood levels of creatinine and urea nitrogen were measured at 2, 4, and 8 weeks. At the fourth week, the different groups were given intragastric administration as follows: The L-HSM and H-HSM groups were given 18 g/ (kg·d)and 36 g/ (kg·d) of Huang Qi-San Qi mixture, respectively. The NDQ group was given 1. 56g/ (kg· d) of NiaoDuqing granules, while the sham and I/ R groups were given the same volume of distilled water. The rats were killed at the 8th week and their kidney and colon tissues were excised. Then, the renal function (serum creatinine and urea nitrogen) was determined and the expression levels of renal fibrosis index proteins (TGF-β1 and α-SMA), inflammatory factors IFN-γ and IL-6, and colonic epithelium tight junction proteins ZO-1, occludin, and claudin-1 were determined. Results Compared with the model group,the high dose of Huang Qi-San Qi mixture effectively restored the damaged renal function,decreased the expression of TGF-β1 and α-SMA proteins, and alleviated renal fibrosis. The high expression of IFN-γ and IL-6 in colonic tissue of the model group was effectively reduced by the low and high dose of Huang Qi-San Qi mixture, and the results of immunohistochemistry and western blot analysis of colonic epithelium tight junction protein showed that,compared with the control group, the expression of IFN-γ and IL-6 in colonic epithelium was higher than that in the sham group. The expression of tight junction proteins ZO-1 and occludin in the model group was significantly decreased, while Huang Qi-San Qi mixture restored the structure of the colon mechanical barrier to some extent. Conclusion Huang Qi-San Qi mixture can prevent and treat CKD rats by improving the structure of the colon mechanical barrier and reducing the expression of inflammatory factors.