Abstract: ob＜x＞jective: We aimed to predict the functioning targets of SM and DKD and construct hierarchical interacting networks for DKD treatment using a DKD rat model and network pharmacological methods.Methods: Bioactive ingredients present in SM were screened using the TCMSP databa＜x＞se. Functioning targets of each active ingredient and those in the DKD were collected. Intersections of the two targets were considered as potential functional targets of SM for DKD treatment. KEGG?analysis revealed that hub genes were enriched in PI3K-Akt?signaling pathway. To test the predicted targets and signaling pathways, a DKD rat model was constructed using a one-time celiac injection of streptozocin (STZ) combined with a high-fat diet. Treatment in the DKD rat model was carried out by intragastric administration of SM for 8 weeks, and the rats were sacrificed. Serum, 24-h urine, and kidney tissues were collected from the rats. Body weight and levels of fasting blood glucose, blood urea nitrogen (BUN), serum creatinine (SCR), and 24-h urinary protein were determined. Kidney tissues were em＜x＞bedded, sliced, and subjected to hematoxylin–eosin and periodic acid–Schiff staining. The ex＜x＞pression of p-PI3K, p-AKT, PI3K, and AKT in kidney tissues was determined by western blotting. Results: The network-ba＜x＞sed pharmacological analysis showed that there were 65 active ingredients in SM. These 65 active ingredients had 170 putative targets and 1,389 putative gene targets for DKD. There were 83 intersections among the putative targets for DKD treatment using SM. PPI network analysis showed that AKT1, IL6, and MAPK1 are putative key target genes. KEGG pathway enrichment analysis showed that the PI3K-AKT signaling pathway probably plays a crucial role. Compared with the DKD rat model, there were apparent changes in the indicators in rats after intragastric SM administration, such as markedly increased body weight and decreased BUN, SCR, and 24-h urinary protein levels. Pathological analysis of kidney tissue sections showed that there was significant injury in DKD rats, and injection of SM alleviated the injury. Western blot assay showed that SM injection increased p-PI3K and p-AKT ex＜x＞pression in kidney tissues. Conclusion: The results of network pharmacology and animal tests reveal that an injection of SM is effective in treating DKD, and the underlying functioning mechanism is probably related to the PI3K-AKT signaling pathway.