Detailed chemical investigation of Terminalia arjuna bark resulted in the isolation and identification of an immunomodulatory constituent, arjunic acid (1), which was converted into seven semi-synthetic derivatives (2-8). All the test compounds in 0.1, 1 and 10 µg/mL concentrations exhibited immunomodulatory effects in a dose dependant manner. 2-O-Lauroyl arjunic acid (3) and 2-O-palmitoyl arjunic acid (4) exhibited immunostimulatory response at all the tested concentrations, while arjunic acid (1), 2,3-di-O-acetyl arjunic acid (2), 2,3-di-O-benzoyl arjunic acid (6), and 2-O-p-anisoyl arjunic acid (7) exhibited immunostimulatory responses at lower doses, whereas at higher concentrations they exhibited immunosuppressive activity. Only 2,3-di-O-palmitoyl arjunic acid (5) showed immunosuppressive activity at all the concentrations; this is being reported for the first time.