To explore the potential inflammatory response mechanism of the Sanhuang Yishen Capsules in the treatment of diabetic nephropathy(DN).Methods:Sixty rats were divided into the normal group,model group,irbesartan group,and low,medium,and high dose Sanhuang Yishen Capsules groups according to the random number table method,with 10 rats in each group.Except for the normal group,the other groups were fed a high-sugar and high-fat diet combined with streptozotocin(STZ) injection to establish a DN model.The normal and model groups were given 2 mL of normal saline via gavage; the irbesartan group was given 11.51 mg/kg of irbesartan via gavage; and the low,medium,and high dose Sanhuang Yishen Capsules groups were given 0.41,0.81,and 1.62 g/kg of Sanhuang Yishen Capsules via gavage,respectively.All groups received the treatments once daily for 4 consecutive weeks.The following indexes among the groups were compared among the groups:fasting blood glucose(FBG),body weight,24-hour urine albumin,renal function indicators,renal histopathological changes,renal tissue oxidative stress-related indicators(SOD,GSH-Px activity,and MDA levels).The expression levels of renal tissue inflammatory mediators［Interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)］,renal tissue inducible nitric oxide synthase(iNOS),renal tissue CD68,CC chemokine receptor 2(CCR2),and renal tissue CC chemokine ligand 2(CCL2),NF-κB P65,p-NF-κB P65,IκB kinase(IκB),p-IκB were also compared among the groups.Results:Compared with the model group,rats in the Sanhuang Yishen Capsules groups had higher body weight and lower levels of FBG,serum creatinine(Cr),blood urea nitrogen(BUN),and 24-hour urine protein.The renal histopathological changes were alleviated,and the activities of SOD and GSH-Px in renal tissues were higher,while the MDA levels were lower.Levels of IL-6,IL-1β,TNF-α,and iNOS in renal tissues were lower.The co-localization level of CCR2 and CD68 in renal tissues was lower,as well as the expressions of CCL2,p-NF-κB P65,and p-IκB proteins.Conclusion:The mechanism of Sanhuang Yishen Capsules in the treatment of DN may be related to the inhibition of NF-κB signaling pathway activation in renal tissues,and the reduction of renal oxidative stress and inflammatory response.