Abstract: Background: Traditional medicine also known as indigenous medicine comprises of knowledge systems that developed over generations within various societies before the era of modern medicine. Aim: This study is aimed at determining the toxicological effect of aqueous extract of M. acuminata on rodent species with specific attempt on acute and sub-acute studies. Methods: Fresh stems of Masularia acuminata were collected dried, pulverized, weighed and mixed with sterile distilled water, mixture left for 72 h and stirred at 3 hourly, filtered and concentrated in a water bath and stored in a refrigerator. Healthy, mature male rats (Rattus norvegicus), weighing between 170-220 g and females, weighing between 155-165 g and mature male and female mice (Mus musculus) weighing between 20-35 g were used for all the experiments. Histological analysis was carried out on the following organs kidney, heart, spleen and liver. Results: Results obtained from the acute toxicity study, indicated that M. acuminata administered via intraperitoneal route, produced an LD50 of 56.23 mg kg-1 while through the oral route produce no sign of toxicity or death in mice at 10,000 mg kg-1, suggesting a LD50 of above 10,000 mg kg-1 via oral route. Thus, referring to the Hodge and Stemer scale, the orally administered extract of M. acuminata could be considered practically non-toxic. The sub-acute treatment indicated that M. acuminata in doses of 500, 1000 and 2500 mg kg-1 per day orally during a 4 weeks consecutive period did not produce any death or any clinical signs of toxicity. Analysis of blood parameters is relevant to risk evaluation of alterations of the haematological system in humans. Conclusion: No significant alterations of the haematological and biochemical parameters of both male and female-treated rats can be attributed to the plant extract. Histologically, there were minimal changes in the kidney comprising mainly of mild interstitial vascular congestion, tissue separation across the dosages and focal (isolated) infiltrates of lymphocytes in the cortex at 2500 mg kg-1. There were minimal changes in the heart, ranging from mild vascular wall thickening (hypertrophyl) at 500, 1000 and 2500 mg kg-1 to mild tissue separation (oedema) at the two higher doses.