Plant medicine, is the oldest form of health care known to mankind. Syzygium guineense is onernof the many species of Ethiopian medicinal plants which have a long history of use as remediesrnfor various ailments such as dysentery, diarrhea and hypertension. In most countries, herbalrnmedicines and related products are introduced into the market without any mandatory safety orrntoxicological evaluation. Therefore this study was conducted to investigate the histopathologicalrneffect of hydromethanol extract of S. guineense on liver and kidney; and blood parameters ofrnrats. For acute toxicity study the rats were randomly divided into three groups (n=4). Therncontrol group received distilled water, while the experimental groups, received 2000 mg/kg andrn5000 mg/kg 80% methanol extract of S.guineense leaves orally. For subacute toxicity study thernrats were randomly divided into three groups (n=6). The control group received distilled water,rnwhile the experimental groups, received 500 and 1500mg/kg 80% methanol extract ofrnS.guineense leaves orally for 28 days. At the end of the experiment, blood samples and liver andrnkidneys were collected for gross pathology, hematology, clinical chemistry and histopathologyrnevaluation. In the acute toxicity study rats treated with 2000 and 5000mg/kg showed norntoxicological signs observed on behavior, gross pathology, and body weight of rats. In thernsubacute toxicity study rats have showed no significant changes on behavior, gross pathology,rnbody weight, hematological and biochemical parameters except glucose (p Ë‚ 0.05) as comparedrnwith the control group. There were no significant differences in the gross and histopathology ofrnthe liver and kidneys of experimental animals in extract exposed groups and their counterpartrncontrol. These results show that hydromethanol extract of S. guineense did not produce adverserneffects in treated rats after acute and subacute treatment. Reduction in serum blood glucose levelrnmay indicate its therapeutic values, but further detailed studies should be carried out tornrecommend its therapeutic use.rnKeywords: Syzygium guineense, medicinal plant, toxicological evaluation