Background of Study: The Kalanchoe genus is a succulent perennial plant belonging to the class Bryophyllum. It thrives at temperate areas of the world. In Africa, over 200 species have being identified and many of these species have been used medicinally especially Kalanchoe pinnata and Kalanchoe integra in Ghana for the treatment of various ailments. Aim/Objective: To evaluate the safety of the aqueous extract of the fresh leaves of K. integra during a single oral high dose of 5000 mg/kg b.wt in ICR mice, a study conducted by the fixed dose method. Research methodology: Freshly prepared aqueous leave extract were strained using muslin and freeze-dried, reconstituted and administered to ICR mice of either sex (21-25 g). The animals were kept under standard conditions and experimental procedure conducted in accordance with animal research guidelines. Blood samples for biochemical analysis were obtained by cardiac puncture. Gross and histopathological examinations were performed and statistical analysis was done using Graphpad Prism 5. Results: No deaths and slight weight increases (p__ampersandsignlt;0.0001) were recorded after the single dose administration of the extract after 14 days. Gross necropsy and histopathology did not reveal any abnormality. Urea levels reduced by 22.3% in males (p__ampersandsignlt; 0.0001) but increased by 21% (p__ampersandsignlt;0.0001) in females compared to the control groups. Plasma creatinine level was decreased in both males 34.0% (P = 0.08) and females 34.3% (p = 0.08) while Alkaline Phosphatase (ALP) levels were significantly higher in the treated males by 19.5% (P = 0.0001) but reduced in females 17.9% (P = 0.158). Conclusion: Kalanchoe integra appears to be non-toxic when administered to ICR mice during a single oral high dose of 5000 mgkg-1 BWT.