Abstract: AIM To study the effect of telmisartan on high glucose and high insulin induced-proliferation of cardiac fibroblasts and its mechanism. METHODSCardiac fibroblasts of suckling Spargue Dawley rats were cultured and randomly divided into control group (5.5 mmol/L glucose), high glucose and high insulin group (25 mmol/L glucose+1×10-7 mol/L insulin), extracellular regulated protein kinase (ERK) inhibitor group (high glucose and high insulin+10 μmol/L PD98059) and telmisartan group (high glucose and high insulin+10 mol/L telmisartan). Forty-eight hours after culture, cell proliferation was detected with cell counting kit-8 (CCK8), cell numbers were measured using crystal violet staining and DNA synthesis was measured using ［3H］thymidine marker. Cell cycle was analyzed using flow cytometry, content of angiotensin II (AngII) and aldosterone (ALD) were measured using ELISA. Protein expression of phosphorylated ERK1/2 (p-ERK1/2) was detected using Western blot. RESULTSCompared with those in control group, cell proliferation (1.43±0.12 vs. 0.50±0.10), cell numbers (1.64±0.03 vs. 1.06±0.02), DNA synthesis (26135.47±324.86 vs. 14528.26±267.18), percentage of S+G2+M ［(19.33±0.12) vs.(8.56±0.07)%］ content of AngII ［(30.58±7.26) vs.(18.26±2.64) pg/ml］ and ALD ［(19.62±1.25) vs.(12.83±1.29) pg/ml］ and protein expression of p-ERK1/2 in high glucose and high insulin group all significantly increased (P<0.05). Compared with those in high glucose and high insulin group, cell proliferation (0.72±0.06 vs. 1.33±0.12), cell numbers (1.35±0.01 vs. 1.64±0.03), DNA synthesis (18643.76±192.52 vs. 26135.47±324.86), percentage of S+G2+M ［(12.84±0.36) vs. (19.33±0.12%)］ content of AngII ［(23.17±5.31) vs.(30.58±7.26) pg/ml］ and ALD ［(15.27±1.13) vs.(19.62±1.25 pg/ml］ and protein expression of p-ERK1/2 in ERK inhibitor group decreased significantly (P<0.05). Compared with those in high glucose and high insulin group, cell proliferation (0.94±0.05 vs. 1.33±0.12), cell numbers (1.49±0.02 vs. 1.64±0.03), DNA synthesis (21829.35±154.73 vs. 26135.47±324.86), percentage of S+G2+M ［(15.13±0.42) vs.(19.33±0.12)%］ content of AngII ［(26.84±4.36) vs.(30.58±7.26) pg/ml］ and ALD ［(17.81±1.53) vs.(19.62±1.25) pg/ml］ and protein expression of p-ERK1/2 significantly decreased (P<0.05). No significant difference was found in the above indexes between ERK inhibitor group and telmisartan group. CONCLUSIONAs the inhibitor of AT1 receptor, telmisartan improves high glucose and high insulin-induced proliferation of cardiac fibroblasts partly through inhibiting the ERK1/2 signaling pathway.