Cissus quadrangularis Linn (C. quadrangularis), or "Phet-Cha-Sung-Khaat" in Thai, is one of the most commonly used medicinal plants in Thailand for the treatment of hemorrhoid; however, the safety of this herb upon long-term consumption has never been reported. Toxicity study was conducted to evaluate the three-month subchronic toxicity of C. quadrangularis powder in five groups of 12 Wistar rats of each sex.Water control group received orally 10 ml of water/kg BW/day. The dried-stems powder was given orally to the four treatment groups at the doses of 0.03, 0.3, 3.0 and 3.0 g/kg BW/day, which were equivalent to 1, 10, 100 and 100 fold of the therapeutic dose in human, respectively, the last group was the recovery group. No difference of initial or final body weights between C. quadrangularis-treated and control groups was detected. It was found that C. quadrangularis did not produce any significant dose-related changes of hematological parameters or serum clinical chemistry, and no histopathological lesion of any internal organ that could be due to the toxic effect of C. quadrangularis was observed. The results indicated that C. quadrangularis at the doses given did not produce any toxicity in the rats during the administration period of 3 months.