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Siddha system is the ancient traditional system of medicine as well as preventive medicine. Poonaga mezhugu (PM) is a Traditional Siddha system of medicine. This medicine is used to oligospermia, impotence, premature ejaculation and nervous weakness. Aim: The aim of the study is to evaluate the acute and sub-acute toxicity of PM on Wistar albino rats. Materials and Methods: In the acute toxicity study test drug was administered to Wistar albino rats into different doses 5, 50, 300 and 2000 mg/kg and then observed individually 1st, 3rd, 4th and 24th hours post-dose on day of dosing and once daily thereafter for 14 days. In Sub-acute toxicity study daily oral doses of 200, 400 and 600 mg per kg body weight of rats was administered for 28 days. The Biochemical and hematology assessments will be carried out the body and relative organ weights of the rats. Results: The PM did not produce any mortality or signs of acute toxicity in the rats tested during the observation period up to 2000 mg/kg. In sub-acute study the results shows no abnormalities in hematological and biochemical parameters and also PM did not alter the kidney function significantly. Conclusion: Our results suggest that No-Observed-Adverse-Effect-Level (NOAEL) of PM is 2000mg/kg in acute toxicity study. It is relatively safe when administered orally in wistar albino rats for long (28 days) administration up to the dose 600 mg/kg.