Aim To investigate the effects and mechanisms of losartan, a specific blocker of angiotensin Ⅱ(Ang Ⅱ) receptor-1 (AT 1R) on vascular remodeling of two-kidney, one-cliped hypertensive rat. Methods The blood pressure (BP),heart weight (HW),and body weight (BW) were determined. The morphologic change of aortas and mesenteric resistance arteries was observed after staining with HE. Western blot was performed to valuate the ERK1/2 activity of aortas. Results The blood pressure,and HW/BW in hypertension group were significantly larger than that of control group (178±17 mm Hg vs 119±11 mm Hg, 0.40±0.07 vs 0.27±0.01 respectively, both p<0.01). Treatment with 20 mg/(kg·d) of losartan normalized BP(132±9 mmHg vs 178±17 mmHg,p<0.05) and HW/BW (0.32±0.03 vs 0.40±0.07,p<0.05). The lumen to media of mesenteric resistance arteries was decreased compared with control group (6.00±0.89 vs 8.96±1.23, p<0.01). Losartan normalized the lumen to media of hypertension group (8.87±1.25 vs 6.00±0.89,p<0.05). The p-ERK1/2 of aortas in hypertension group was overexpression compared with control group, and the overexpression of p-ERK1/2 was downregulated by treatment with losartan. Conclusion Losartan could regulate vascular remodeling in 2-kidney,1-cliped hypertensive rat by inhibiting the signaling pathway of ERK1/2.