Objective To observe the effect of Sanqi Oral Liquid on the podocytes and the expression of slit diaphragm-associated molecules (including Nephrin, Podocin and CD2AP proteins) of diabetes mellitus (DM) rats after unilateral nephrectomy, so as to explore its mechanism for protecting renal function. Methods SD male rats were randomized into sham operation group, model group and Chinese medicine group. The experimental diabetes mellitus ( DM) model was given unilateral nephrectomy and intraperitoneal injection of 35 mg/kg of streptozocin (STZ). And then the model rats were given intragastric administration of Sanqi Oral Liquid (2.5 g· kg-1·d-1) and the same volume distilled water respectively for 8 weeks. After treatment, the density of podocytes and the podocytic foot process width of different groups were measured. Immunohistochemistry was used to observe the changes of the expression of Nephrin, Podocin and CD2AP in renal tissues of different groups. Results After treatment with Sanqi Oral Liquid, the density of podocytes was increased, the foot process lesion was relieved, and the expression levels of Nephrin, Podocin and CD2AP proteins were increased (P<0.05 or P<0.01 as compared with those in the model group). Conclusion The protective mechanism of Sanqi Oral Liquid for renal function of unilateral nephrectomy DM rats is possibly related with the alleviation of podocyte injury and with the regulation of the expression of Nephrin, Podocin and CD2AP proteins in podocytes.