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Context: Lansium domesticum Corrêa is a higher plant belonging to Meliaceae family and widely distributed in South East Asia. The leave extract of Lansium domesticum cv kokossan contains 9,19-cyclolanost-24-en-3-one,21,23-epoxy-21,22-dihydroxy (21R, 22S, 23S), which has shown a strong cytotoxic activity (IC50 = 1.13 ppm) against MCF-7 breast cancer cells. Aims: To evaluate the acute toxicity of ethanol extract of L. domesticum cv kokossan leaves in female Wistar rats. Methods: Acute oral toxicity test was done based on OECD 425:2006 guidelines, consisting of a limit and main tests. The limit test was conducted at a dose of 5000 mg/kg, whereas the main test consisted of ten treatments, including control, with five replications each. Results: The results showed a strong negative correlation between dose of the extract and the weight gain of tested animals (r = -0.93). The administration of the extract increased the relative weight of organs, i.e. liver and brain, only at a high dose. Histopathological examination showed an increasing of necrotic cells as well as disruption of tissue architectural of all organs in a dose-dependent manner. However, the toxic signs and organ damage did not show significantly different compared to control. The LD50 value estimated by Probit analysis was 16538.49 mg/kg BW for ethanol extract, which categorized as relatively harmless. Conclusions: The data obtained from this study revealed that the ethanolic extract of L. domesticum cv kokossan leaves was relatively harmless to female Wistar rats. However moderate histopathological toxicity sign appeared in all examined organs. Thus, further study is needed to evaluate the effect of long-term exposure.