In order to explore the protective effect of metformin mediated nuclear factor-κB (NF-κB) signaling pathway on thedamage of diabetic nephropathy cells, HGPC cells were cultured in vitro and treated with 10, 20, 30 and 40 mmol/L D-glucoseto select the optimal concentration of D-glucose for the construction of HGPC hyperglycemic inflammatory injury model. Then20, 40, 80 and 160 mmol/L metformin were used for intervention, and the optimal concentration of metformin was screened.The cells were then divided into control group (Con group), high glucose group (HG group) and metformin group (Met group,30 mmol/L D-glucose+80 mmol/L metformin), inhibitor group (Y group, 30 mmol/L D-glucose+1 μmol/L NF-κB pathway inhibitor BAY 11-7082), metformin+inhibitor group (Met+Y group, 30 mmol/L D-glucose+80 mmol/L metformin+1 μmol/LBAY 11-7082) and metformin+agonist groups (Met+A group, 30 mmol/L D-glucose+80 mmol/L metformin+1 μmol/L NF-κBpathway agonist Prostratin), intervention was conducted for 24 h. Cell count kit 8 (CCK-8) was used to detect cell viability；theexpression levels of inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA)；cell invasion andmigration were determined by Transwell assay. Western blotting (WB) was used to detect the expression levels of E-cadherin,N-cadherin, vimentin, Fibronectin (FN), NF-κB p65 and p-NF-κB p65. The results show that: HGPC cells were treated with30 mmol/L D-glucose for 24 h to construct HGPC hyperglycemic inflammation model, and 80 mmol/L was the optimal concentration of metformin. Compared with Con group, the levels of inflammatory cytokines tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β), invasion ability, migration ability, the expression levels of N-cadherin, vimentin, FN and p-NF-κB p65protein in HG group significantly increased, while the expression level of E-cadherin protein decreased (P<0.05). Comparedwith HG group, the levels of inflammatory cytokines TNF-α, IL-1β, cell invasion ability, migration ability, the expression levels of N-cadherin, vimentin, FN and p-NF-κB p65 protein in Met group and Y group significantly decreased, and the expressionlevel of E-cadherin protein increased (P<0.05). Compared with the Met group, the above indexes changed more significantlyafter the addition of BAY 11-7082 (P<0.05), and the trend of Met+A group was opposite to that of Met+Y group (P<0.05).Metformin inhibits D-glucose-induced HGPC inflammatory response, invasion, migration and epithelial-mesenchymal transitionprocess by blocking the activation of NF-κB pathway, and protects podocyte injury induced by high glucose.