Cynancum aculum L.(Asceleapidaceace) is a wild plant grown in Egypt and used for healing mouth ulcer in Folk medicine. The intraperitoneal (I.P.) LD(50) doses in rats were: 5.87 and 4.2 g./Kg.b.w. for total alcoholic and crude alkaloid extracts respectively. The toxic symptoms in both extracts were loss of appetite, increasing respiratory rate, abdominal convulsion, then general paralysis and death. Sub-acute toxicity was performed, using 6 groups of rats. The first two groups were fed a diet containing 10-20% dried leaves of C. aculum and the 3rd group was kept as a control. Meanwhile, the 4th & 5th groups were I.P. injected with 1/5 & 1/10 LD(50) of crude alkaloid extract and the 6th group served as a control saline. 45 days post-daily treatment blood samples and specimens of different organs were collected for haematological and histopathological examinations. Anaemia was observed in 20% fed group, and the two injected groups with crude alkaloid extract. Also, leucopenia and lymphocytopenia were obtained in such groups. Moreover, there was no major histopathological changes in the examined tissues. Only,mild alterations were observed in different organs (kidney, lung spleen, ovary and testes). On the other hand, the 1/5 LD(50) of crude alkaloid extract caused degenerative changes in the liver tissues of the treated rats. The present study concluded that C. aculum L. is more safe than other members of the same family. it has minimal harmful effects on different tissues even in higher doses. So it can be used safely in patent medical preparations.