Prosopis juliflora (Mathenge) is an exotic, evergreen leguminous plant found in the dry Coastal, Rift Valley and Northern parts of Kenya. It is tolerant to extreme environmental conditions, rated among top 100 most invasive species worldwide. The species leaf extracts is used in folk cure to various ailments and have promising pharmacological properties however; information on their toxicity in animals and human is insufficient. The study assessed phytochemical composition of P. juliflora leaf extracts, effects on body weights, organ weights, hematological parameters, liver function markers and histopathology in major organs of Wistar albino rats. Acute toxicity test was carried out at 2000 mg/kg body weight followed by a 28 days sub chronic toxicity study at 100, 350 and 1000 mg/kg body weight extracts dosages. The control animals were administered with normal saline. Animals were monitored for physical and behavioral changes including death. They were fasted overnight on 28th day and sacrificed on anesthesia on 29th day. Blood was collected by cardiac puncture. Hematological and liver functions tests were done. Tissue sample of selected organs were processed for histopathology. Data from control and treated animals groups were analyzed by ANOVA and Dunnett's test. Phytochemicals confirmed included alkaloids, flavonoids, phenols, tannins, terpenoids and saponnins but no cardiac glycosides. Median lethal dose was estimated at above 2000 mg/kg body weight. Dose related transient toxicity symptoms included wheezing, decreased activity, and pilo erection. No significant toxicity effects on hematological parameters were noticed except in mean platelets volume. Similarly, no significant adverse effects occurred in liver function tests except at 1000 mg/kg body weight dosage. No significant adverse changes in plasma proteins, body weights and absolute organ weights were observed except in kidneys and spleen. Histological examination of sample tissues showed mild effects in spleen and kidneys but no adverse pathology in other organ tissues.