Simarouba glauca has been widely reported to be effective against a number of diseases and possesses medicinal benefits. Thus, the study was conducted to evaluate the toxic effect of aqueous leaf extract of Simarouba glauca (AESG) on relevant organs of male Wistar rats. The oral acute toxicity of AESG was evaluated according to the method described by Lorke. Sub-chronic toxicity of AESG was carried out in line with the guidelines of the Organization for Economic Co-operation and Development (OECD), using a total of twenty-four (24) male Wistar rats divided into four groups of six rats each. Test rats were orally administered AESG at doses of 500, 1000 and 2000 mg /kg body weight, respectively, daily for thirty (30) days. At the end of the study, rats were fasted overnight and sacrificed; the relevant biochemical and histopathology evaluation was carried out. Statistical analysis was conducted using the GraphPad Prism®, version 7. The data obtained indicated that the LD₅₀ exceeded 5000 mg/kg. There were significant increases (P < 0.05) in percentage (%) body weight of test rats. There were no significant differences (P < 0.05) in mean liver, kidney, and heart weight/body weight (IOW/BWT) ratios. The AST activity was significantly lowered (P < 0.05) in rats administered AESG 2000 mg/kg. The ALP activities were significantly elevated (P < 0.05), while the GGT activities were significantly lowered (P < 0.05) in all groups of rats administered AESG. Plasma conjugated and unconjugated bilirubin were significantly lowered and elevated (P < 0.05), respectively in rats administered AESG 1000 and 2000 mg/kg. Plasma urea was significantly elevated (P < 0.05) in rats given AESG 1000 mg/kg. Test rats given AESG 2000 mg/kg recorded significant reduction (P < 0.05) in plasma sodium ions concentration. Rats given AESG 500 mg/kg recorded significant reduction (P < 0.05) in plasma bicarbonate ion levels. The findings suggest that AESG was not significantly toxic to the liver, kidney, and heart.

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