Used of Immunomodulator and anti-inflammatory drug is a new application in the treatment disease. The most immunomodulator and anti-inflammatory was from medicinal plants. Mentha pulegium L (MTH) is traditional medicinal plant widely used in the world, in this study investigated the Immunomodulatory and anti-inflammatory activity of MTH leaves ethanol extract and its fractions with the effect of angiogenesis cytokine gene expression and production. Macrophage RAW 264.7 cell was used to investigate the Immunomodulatory and anti-inflammatory effect both MTH leaves extract and fractions. The results were showed significant increase in the viability of treated RAW 264.7 cell with MTH leaves extract and fraction1 and inhibited Nitric oxide production, while enhancement the production of angiogenesis cytokine and increased intracellular production of INF- , IL6 and IL8 in dose dependent manner. In conclusion of the outcome the M. pulegium L leaves extract be as new Immunomodulation and anti-inflammatorydrug.