This study investigated the effect of the angiotensin-converting enzyme (ACE) inhibitor perindopril on left ventricular (LV) remodeling and cardiac function in rats with aortic regurgitation (AR). Twenty male Sprague-Dawley rats in which AR was produced by closed-chest aortic valve puncture were divided into untreated and perindopril-treated (5 mg/kg/day) rats. Ten control rats were sham-operated. Blood pressure, body weight, and echocardiographic recordings were followed every 2 weeks for a period of 12 weeks. LV dimension (LVD) and fractional shortening (FS) were calculated. The heart was finally excised for weight, hydroxyproline measurements, and histopathology. At 12 weeks, end-diastolic LVD increased in untreated rats (10.8 +/- 0.2 mm) but did not dilate in treated rats (9.6 +/- 0.3 mm, p < 0.01 vs untreated rats). FS decreased from 6 weeks in untreated rats (27.3 +/- 0.9% at 12 weeks), but did not change in treated rats (33.8 +/- 0.5%, p < 0.001). The ratio of LV weight to body weight in untreated rats (2.62 +/- 0.11 mg/g, p < 0.05) was higher than in sham-operated rats (1.52 +/- 0.02 mg/g) and than in treated rats (1.95 +/- 0.07 mg/g). Interstitial collagen accumulation histopathologically increased in untreated rats and was inhibited in treated rats. LV collagen of untreated rats (1.46 +/- 0.08 mg/100 mg, p = 0.03) was higher than those of treated (1.08 +/- 0.09 mg/100 mg) and sham-operated rats (1.06 +/- 0.14 mg/100 mg). Perindopril inhibited LV remodeling induced by volume overload and preserved LV function in AR rats.