Objective To explore the therapeutic effect and potential mechanism of action of Astragalus propinquus Schischkin and Panax notoginseng ( A&P ) compound in a mouse model of diabetic nephropathy ( DN). Methods Fifty male C57BL/ 6 mice were randomly divided into normal, model, L-A&P, H-A&P and irbesartan groups. Mice were fed a high-fat, high-sugar diet for 2 months, and streptozotocin 50 mg / (kg·d) was intraperitoneally injected for 5 days to induce DN. Different gavage treatments were given to the groups. After 4 weeks of treatment, mice were killed and materials collected. Renal pathology was observed using hematoxylin-eosin and periodic acid – Schiff stained sections. Renal function and the expression of Arid2-IR lncRNA, inflammatory factors [ tumor necrosis factor-α ( TNF-α), interleukin-1β (IL-1β), IL-6], and NF-κB and its downstream signaling molecules were examined. Results The 24 h urine protein, serum creatinine, and urea nitrogen levels were significantly decreased in A&P-treated mice compared with the DN group, which suggests that renal function recovered to a certain extent. Renal pathology was significantly improved, and IL-1β, IL-6 and TNF-α expression decreased in a dose-dependent manner. Expression levels of Arid2-IR and NF-κB and its downstream molecules ( COX2, IL-6) were down-regulated, indicating that activation of the NF-κB signaling pathway was inhibited. Conclusions A&P reduced kidney inflammation in mice with DN, and its mechanism of action may be related to the regulation of Arid2-IR/ NF-κB signaling.