Objective: The objective of the present study was to evaluate the immunomodulatory activity of the roots of Atalantia monophylla. In the present study Pet. Ether, Chloroform and Methanolic fractions of the ethanolic extract of the roots of Atalantia monophylla, were administered orally, in the doses of 10 mg/kg and 30 mg/kg, to evaluate the immunomodulatory activity. Materials and Methods: The Methanolic fraction showed most significant effect when compared with control group, in the dose of 30 mg/kg, in the E.Coli induced abdominal sepsis and Carbon Clearence Test as models for non-specific immune response. In the models of the Specific immune response, cell mediated immune response to SRBC-delayed type of hypersensitivity (DTH) the methanolic fraction in the dose 30 mg/kg, when compared with control group, showed most significant effect on decrease in footpad edema after treatment. Results: Humoral immune response was assessed by Sheep erythrocyte agglutination test, in which the Methanolic fraction of Atalantia monophylla in the dose of 30 mg/kg showed most significant (p<0.05) increase in antibody titer after treatment when compared with control group. Conclusion: The present investigation reports that the Methanolic fraction of the ethanolic extract of the roots of Atalantia monophylla, in the dose of 30 mg/kg showed most significant immunomodulatory activity.