Abstract: The toxicity of Piper guineese extract, known as a spice and seasoning and also used in treatment of different ailment such as malaria was investigated in rats. Twenty four wistar rats were obtained, weighed and divided into four groups of six per group. They were allowed access to rat feed and tap water ad- libitum for two weeks period of acclimatization. Different concentrations of Piper guineese extract were administered to three of the experimental groups. 25, 50 and 75 mg/100 g, while the fourth group received 100% tap water and served as control. The study lasted 21 days. The results obtained showed slightly reduced agility, loss of appetite in animals treated with higher concentration of extract. Sections through the kidneys and livers of the sacrificed animals showed alteration of their normal cyto-architecture, some of which were pathological. The result of the present study suggests that Piper guineese could be toxic at certain dosage and over prolonged periods.