Objective To investigate whether the effect of transient high glucose on inflammatory factors expression could be continuous in rat glomerular mesangial cell, and its relation with histone methylation modification. Methods Rat glomerular mesangial cells (HBZY-1) were divided into three groups: the high glucose group (25.0 mmol/L glucose), the hypertonic group (MA, 5.5 mmol/L glucose+19.5 mmol/L mannitol) and the normal-glucose control group (5.5 mmol/L glucose), which were cultured for 24 h respectively. All 3 groups were then changed with normal-glucose medium to culture for 24 h, 48 h and 72 h. Their protein, mRNA and supernatant were harvested. The protein expressions of mono-methylation of H3 lysine 4 (H3K4me1) was measured by Western blotting, and the mRNA expressions of NF-κB subunit p65 and set7/9 were determined by real time-quantitative PCR. The expression of monocyte chemoattractant protein 1 (MCP-1) and vascular cell adhesion molecule 1 (VCAM-1) were detected by enzyme-linked immunosorbent assay. Results (1) Compared with those in normal control group, the expressions of H3K4me1 protein and set7/9 mRNA were first up-regulated in high glucose group, then gradually down-regulated in the following 48 h normal-glucose medium (as compared with those at 0 h, all P＜0.05). At 72 h there was no statistic difference between high glucose group and normal control group (all P＞0.05). (2) Compared with those in normal control group, the up-regulated p65 mRNA, VCAM-1 and MCP-1 sustained at least for 72 h in high glucose group. Conclusions Transient high glucose can induce persistent inflammatory factors expression in rat glomerular mesangial cells, which may via histone modification.