Chlorella are traditionally freshwater green algae that have been evaluated for dietary purposes because of their nutritional value. This study investigates the safety of Chlorella protothecoides in a 28-day study. Sprague-Dawley rats were administered 0 (control), 2.5, 5.0, or 10% of their diet for 28days using an FDA Redbook protocol. The average daily dietary intake of algal biomass was determined to be 0, 1794, 3667, and 7557 mg/kg body weight for males and 0, 1867, 3918, and 8068 mg/kg body weight for females. Hematological and biochemical analyses were conducted, and upon completion, gross and microscopic evaluations were performed. No signs of toxicity were observed. Although statistically significant alterations were noted in several parameters among males and females, these changes were deemed to be of no toxicological significance due to the lack of dose-response relationships, the fact that they occurred in only one sex, and the lack of any supporting gross or microscopic alterations. The no-observed-adverse-effect level for the algal biomass under the conditions of this study was considered to be 10% in the diet, the highest dose tested.