Medicinal combinations of Isaria japonica (Paecilomyces tenuipes, Paecilomyces japonica, and Isaria tenuipes) and the silkworm Bombyx mori are commercially available in Japan, China, and Korea. Isaria japonica exhibits host specificity for lepidopteran insects and can be cultured in the insect’s body. Recently, a hot-water extract of an I. japonica product (“IJE”) was shown to prevent brain function decline in aging mice. Therefore, evaluating the safety profile of IJE is worthwhile. Acute toxicity experiments were performed on adult female ICR mice (8-10 weeks old; 25-35 g). Sub-chronic toxicity experiments on adult female Wistar rats (8-10 weeks old; 130-150 g) assessed general behavior, mortality, body weight, food + water consumption, hematology, blood chemistry, relative organ weights and histopathology. IJE caused neither significant visible signs of toxicity nor mortality in ICR mice. In the sub-chronic toxicity analysis, administration of IJE to Wistar rats at doses of 25 and 500 mg/kg for 28 consecutive days did not cause mortality. No significant differences were found in food or water consumption, hematological parameters, or relative organ weights between the treated and control groups. IJE appears to be safe when administered orally.