The posttranslational modification of proteins by small ubiquitin-like modifiers (SUMOs) has emerged as an important regulatory mechanism for the alteration of protein activity, stability, and cellular localization. The latest research demonstrates that sumoylation is extensively involved in the regulation of the nuclear factor kappa B (NF-kappa B) pathway, which plays a critical role in the regulation of inflammation and contributes to fibrosis in diabetic nephropathy (DN). However, the role of sumoylation in the regulation of NF-kappa B signaling in DN is still unclear. In the present study, we cultured rat glomerular mesangial cells (GMCs) stimulated by high glucose and divided GMCs into six groups: normal glucose group (5.6 mmol/L), high glucose groups (10, 20, and 30 mmol/L), mannitol group (i.e., osmotic control group), and MG132 intervention group (30 mmol/L glucose with MG132, a proteasome inhibitor). The expression of SUMO( SUMO2/3, I kappa B alpha, NF-kappa Bp65, and monocyte chemotactic protein 1 (MCP-1) was measured by Western blot, reverse-transcription polymerase chain reaction, and indirect immunofluorescence laser scanning confocal microscopy. The interaction between SUMO1, SUMO2/3, and I kappa B alpha was observed by co-immunoprecipitation. The results showed that the expression of SUMO1 and SUMO2/3 was dose-and time-dependently enhanced by high glucose (p < 0.05). However, the expression of I kappa B alpha sumoylation in high glucose was significantly decreased compared with the normal glucose group (p < 0.05). The expression of last was dose- and time-dependently decreased, and NF-kappa Bp65 and MCP-1 were increased under high glucose conditions, which could be mostly reversed by adding MG132 (p < 0.05). The present results support the hypothesis that high glucose may activate NF-kappa B inflammatory signaling through I kappa B alpha sumoylation and ubiquitination. (C) 2013 Elsevier Inc. All rights reserved.