Background: The role of the Angiotensin II type 2 receptor (AT2) in cardiac hypertrophy remains controversial. Here we studied the effects of AT2 on chronic pressure overload-induced cardiac hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes. Methods: Left ventricular hypertrophy was induced by banding of the ascending aorta (AS). Transgenic mice overexpressing AT2 (AT2TG-AS) and non-transgenic mice (NTG-AS) were studied after 70 days of aortic banding. Non-banded NTG mice were used as controls. Left ventricular (LV) function was determined by catheterization via LV puncture and cardiac magnetic resonance imaging. LV myocyte diameter and interstitial collagen were determined by confocal microscopy. ANP and BNP were analyzed by Northern blot. SERCA2, iNOS, eNOS, ERK1/2, P70S6K, SHP-1 and PP2A were analyzed by Western blot. Results: LV myocyte diameter and collagen were significantly reduced in AT2TG-AS compared to NTG-AS mice. LV anterior and posterior wall thickness were not different between AT2TG-AS and NTG-AS mice. LV systolic and diastolic dimensions were significantly higher in AT2TG-AS than in NTG-AS mice. LV systolic pressure and LV end-diastolic pressure were lower in AT2TG-AS than in NTG-AS mice. ANP and BNP were not different between AT2TG-AS and NTG-AS mice. SERCA2 was not different between AT2TG-AS and NTG-AS mice. PLB and the PLB/ SERCA2 ratio were significantly higher in AT2TG-AS than in NTG-AS mice. iNOS was higher in AT2TG-AS than in NTG-AS mice but not significantly different. Conclusion: Our results indicate that AT2 receptor overexpression modified the pathological hypertrophic response to aortic banding in transgenic mice.