This study evaluates the effects of age and chronic dietary restriction (DR) on nonneoplastic diseases in rats that were fed the American Institute of Nutrition (AIN)-93M purified diet. Male Sprague-Dawley (SD) rats were divided into an ad libitum (AL) group and a DR group that was fed the AIN-93M diet with intake reduced by 31%. Nonneoplastic disease profiles were developed to clarify whether the AIN-93M diet fulfills long-term nutritional requirements of rats. Subsets of rats were killed at 58 and 114 weeks of age, and histopathology was performed. At 58 weeks of age, the 2 main types of nonneoplastic diseases in AL rats were liver vacuolization and cardiomyopathy. Dietary restriction reduced the severity and incidence of both lesions. At 114 weeks of age, the most common lesions in AL rats were cardiomyopathy, nephropathy, liver vacuolization, and degeneration with renal failure and genitourinary infections causing the greatest mortality. Dietary restriction reduced the incidence and severity of these lesions. Nonneoplastic diseases accounted for 28.9% and 0.0% of total mortalities in the AL and DR groups, respectively; however, there was a higher incidence of unknown deaths in the DR rats (52.6%) compared to AL rats (28.9%), which may have limited the success of DR to improve survival. Although the AIN-93M diet supported chronic rat growth, alterations in some dietary component concentrations may be required to lower body weight in chronic rodent and human studies. Factors such as diet composition and digestibility may alter nonneoplastic diseases and mortality in rats and humans in a similar fashion.