Objective: To investigate the safety levels of hydromethanol leaf extract of Helianthus annuus Linn. (H. annuus) in rat. Methods: Acute oral toxicity test of hydromethanol leaf extract of H. annuus was conducted through up and down method at 2.00 g/kg dose limit in rats. The chronic toxicity study was conducted by administering different concentrations (0.25, 0.50 and 1.00 g/kg) of hydromethanol extract of H. annuus in feed, for 90 consecutive days. On days 30, 60 and 90, blood samples were collected from the retro-orbital plexus of the rats for determination of serum biochemical parameters. Histopathological examination of the pancreas, livers, kidneys and testis were also conducted. Results: The LD50 of the hydromethanol extract of H. annuus was greater than 2.00 g/kg and it significantly (P < 0.05) reduced serum cholesterol. On days 60 and 90, the serum urea and creatinine levels of hydromethanol extract of H. annuus treated groups were elevated when compared with the control group. There were fibrosis in the kidneys and livers; degeneration and necrosis in the testis and significant dose-dependent increases in number and size of pancreatic islet of langerhans. Conclusions: The findings suggest that hydromethanol extract of H. annuus is tolerated in short term administration, but long term (up to 90 days) administration at high doses, may elicit hepatic, testicular and nephrotic disorder.