The acute and sub-acute toxicity studies of ethyl acetate root extract of Guiera senegalensis was carried out in rats. Administration of 80,1600 and 3200 mg/kg body weight of the ethyl acetate root extract produced 20,80 and 100 % mortality in rats respectively. The calculated LD50 was 1160 mg/kg body weight. There was a statistically significant increase in the intestine body weight ratio with mean of( 1.27±0.21 %) of the group given 400 mg/kg body weight of the extract relative to the control with mean of (0.75±0.13 %). There was an increase in the RBC count of the extract (400 mg /kg) treated group with mean value of 8.15 + 0.45 x 106 /mm3 when compared with the control group with mean value of 7.10 + 0.05 x 106 /mm 3. The WBC count also increased significantly when the control group with mean value of 10.55+50. 00 x 103 /mm3 were compared with the extract treated group with mean values of 12.75 ± 50.00, 14.45 ± 50.00 and 17.65 ± 50.00 x 103/mm3 respectively. The differential leucocyte count analysis showed that there was an increase in the lymphocyte, monocyte and neutrophil count which was statistically significant. There was a slight decrease (4.15 ± 0.47 mg/dl) in the urea concentration of the group given the dose of 400 mg/kg of the extract which was statistically significant (p<0.05). The histopathologic examination of the organs of rats harvested from the sub-acute studies (liver, kidney and intestine) of extract treated groups when compared with the control group revealed some histologic lesions which included congestion of central vein of liver, mild hydrophobic change in the tubular lumen and interstitial nuclear cell infiltration of the kidney and globlet cell hyperplasia of the intestine in rats. These lesions were observed to be pronounced in the in group treated with 400 mg/kg body weight of the ethyl acetate extract. In conclusion, the study established the safety of ethyl acetate root extract of G. senegalensis and thus could be used at lower doses as an antidiarrhoeal drug.