Objective To observe the activity of extracellular signal-regulated kinase（ERK） in glomerular mesangial cells（GMC）exposed to high glucose and the effect of valsartan on ERK activity, and explore the possible renoprotection mechanism of valsartan.Methods GMC were cultured in vitro and the groups were designed as follows: low glucose group（NG, 5.5 mmol/L d-glucose）, high glucose group（HG, 30 mmol/L d-glucose）, valsartan group（HG+val, 30 mmol/L d-glucose+valsartan 10 μmol/L） and mannitol group（MG, 24.5 mmol/L mannitol +5.5 mmol/L d-glucose）. The expression of phosphate (p-) ERK1/2 protein was detected by immunocytochemical technique and Western blot. RT-PCR and radioimmunoassay were respectively used to measure the expression of TGF-β1 mRNA in mesangial cells and the content of type Ⅳ collagen in supernatant. Results The strongly positive staining of p-ERK1/2 in mesangial cells exposed to high glucose was observed not only in cytoplasm, but also in nuclei at 12 h, with an increasing tendency to 72 h (P < 0.01). The level of TGF-β1 mRNA in mesangial cells and the content of type Ⅳ collagen in the supernatant of HG group were also significantly higher than those of NG group (P < 0.01). Compared with those in HG group, the above parameters were significantly down-regulated in HG+val group (P < 0.01), whereas there were no significant differences of above parameters between MG group and NG group. Conclusion The expression of p-ERK1/2 is up-regulated in GMC exposed to high glucose medium, which can be inhibited by valsartan.