The aim of this study was to investigate the roles of AMP-activated protein kinase α subunit (AMPKα), hypersensitive C-reactive protein (hs-CRP) and Fcγ receptor (FcγR) in diabetic nephropathy and drug intervention effects. Sixty Sprague Dawley male rats were randomly divided into the control (n=30) and observation (n=30) groups. The model of type 2 diabetic nephropathy was established by high-fat and high-glucose diet and streptozotocin injection. The rats in the observation group were treated with baicalein and the rats in control group did not receive any drug intervention. The pathological changes of kidneys were observed by hematoxylin and eosin (H&E) staining. The expression of AMPKα mRNA in renal tissue was detected by reverse transcription-polymerase chain reaction (RT-PCR). The levels of hs-CRP and FcγR were measured by enzyme-linked immunosorbent assay (ELISA) at 1, 4, 6 and 8 weeks after drug intervention and blood urea nitrogen (BUN) and the 24 h urinary micro-albumin (U-ALB) levels were compared at 1, 4, 6 and 8 weeks after intervention. After 8 weeks of drug intervention, the pathological changes of kidneys in the observation group were significantly lower than those in the control group (p<0.05), while the relative expression levels of AMPKα mRNA and protein in the control group were higher than those in the observation group (p<0.05). The levels of hs-CRP, BUN and 24 h U-ALB in the control group were significantly higher than those in the observation group at different time-points after drug intervention and the level of FcγR in the control group was significantly lower than that in the observation group (p<0.05). Baicalein may protect renal function by inhibiting the expression of AMPKα and inflammatory reaction, and can also decrease BUN and 24 h U-ALB levels and improve the pathological changes of the kidney.